REUMADAGARNA 2014 - Svensk Reumatologisk Förening

Transcription

ReumaBulletinen
tidskrift för svensk reumatologisk förening • nummer 96 • 2/2014
REUMADAGARNA 2014
Program Abstracts
Innehåll · 2/2014
ReumaBulletinen
ReumaBulletinen är Svensk Reumatologisk Förenings
tidskrift och utkommer med sju nummer per år
Ansvarig utgivare Ralph Nisell
Reumatologiska kliniken
Karolinska Universitetssjh
171 76 Stockholm
Tel 08-517 760 93
[email protected]
Redaktör
Tomas Bremell
Reumatologi
Sahlgrenska Universitetssjh
Gröna Stråket 12
413 45 Göteborg
Tel 031-342 33 78
[email protected]
3
Välkommen till Reumadagarna i Örebro
4
Reumatologkliniken vid Örebro
universitetssjukhus
10Mötesprogram
14 Reumadagarna 2014 - Abstracts
48 Reumakalender
Red.medlemmar
Ido Leden
[email protected]
Bengt Lindell
[email protected]
Milad Rizk
[email protected]
Ioannis Parodis
[email protected]
Produktion
Mediahuset i Göteborg AB
Marieholmsgatan 10C
415 02 Göteborg
www.mediahuset.se
Tel 031-7071930
Annonser
Dan Johansson
[email protected]
Olle Lundblad
[email protected]
Layout
Eva-Lotta Emilsdotter
[email protected]
Tryck
Åkessons Tryckeri AB
Box 148
361 22 Emmaboda
www.akessonstryck.se
Distribution
Distribueras som posttidning
ISSN 2000-2246 (Print)
ISSN 2001-8061 (Online)
Utgivningsplan 2014
Nummer
Manusstopp
Utgivning
Nr 1 RB
Nr 2 RB
Nr 3 RB Vetenskap
Nr 4 RB
Nr 5 RB
Nr 6 RB Vetenskap
Nr 7 RB
24 januari
7 februari
7 mars
22 april
1 september
30 september
10 november
28 februari
19 mars
16 april
28 maj
8 oktober
5 november
18 december
Omslagsbild:
Tidig bokskog Skäralid, Skåne Foto: Sven-Olov Ohlsson, Kristianstad
www.svenskreumatologi.se
ReumaBulletinen Nr 96 · 2/2014
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Nationella ST-läkardagarna 2014
ST-läkardagarna kommer att äga rum måndag 19 maj från kl. 12.00 till tisdag 20 maj kl. 14.30 i Hotell Gamla Fängelset, Storgatan 62, Umeå
Tema Infektioner – som orsak eller verkan
Det blir intressanta föreläsningar av infektionsläkare, lungläkare, neurolog och reumatologer. Vi kommer också att
diskutera patientfall och deltagare som så önskar är välkomna att anmäla fall för diskussion.Vi får också aktuell information av Svensk Reumatologisk Förenings (SRF:s) nya Yngreläkarrepresentant Yulia Stennikova.
Kostnad: Hemmakliniken står för resekostnaden och anmälningsavgift. 500 SEK för medlem i SRF, 2000 SEK för ickeSRF-medlem. Anmälningsavgiften återbetalas ej vid sen avanmälan.
Mer detaljerat schema och anmälningsblankett kommer som länk på SRF:s hemsida under februari månad.
Välkomna till två givande dagar i Europas kulturhuvudstad 2014!
Ewa Berglin ST-studierektor Reumatologiska kliniken
Norrlands Universitetssjukhus
[email protected]
070-286 45 49
2
Lotta Ljung
Överläkare
ORDFÖRANDE · Ralph Nisell
Välkommen till
Reumadagarna i Örebro
(USÖ). Även SveReFo, FRS (reuma-sjuksköterskorna) och Reumatikerförbundet har
parallella program under onsdagen och torsdagen. Vi tycker att agendan ser mycket
spännande ut och vi hoppas på bra och givande Reumadagar 2014. Du är mycket välkommen, och hoppas vi ses i Örebro!
Ska vi kalla vårt årliga reumatologiska
möte som vi tidigare har benämnt ”Vårmötet” för ”Reumatologi-dagarna” eller
något enklare för ”Reumadagarna”? Eller ska det rent av vara ”veckan” istället
för ”dagarna”?
D
essa frågor ställde sig Svensk Reumatologisk Förenings (SRFs) styrelse för ett år sedan.
Orsaken till namnbytet var två, dels ville vi
markera att något nytt har hänt, dels infaller det framöver återkommande reumatologiska mötet i månadsskiftet augusti/september med start 2015. Specialnummer
Detta nummer av Reumabulletinen, nr 2,
är ett specialnummer och har helt fokus
på Reumadagarna, som i år således hålls i
Örebro den 1-4 april. Det är första gången
vårt svenska reumatologi-möte pågår under fyra dagar.
Att mötet nu har förlängts beror på att det
vetenskapliga programmet har flyttats från
Riksstämman till dessa Reumadagar. Detta
innebär att reumatologiska abstracts och
posters vilka tidigare år har presenterats i
månadsskiftet november/december (Riksstämman) nu istället kommer med på detta
möte. Notera dessutom att föreläsningar,
För mer information var god se:
www.reumadagarna2014.se
Vår-reuma-hälsningar!
”Reumadagarna hålls i
Örebro den 1-4 april”
prisutdelningar, mm också har flyttats till
Reumadagarna. Spännande agenda
”Reumadagarna 2014” arrangeras i samarbete med SRF och den Reumatologiska kliniken på Universitetssjukhuset i Örebro
Ralph Nisell
Ordf SRF
Boel Mörck
Vice ordf SRF
Christopher Sjöwall
Vetensk sekr SRF
Marie Vallgårda
Lokalt ansvarig Reumadagarna
Sara Bucher
Vchef Reumatologiska kliniken USÖ
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REUMATOLOGKLINIKEN I ÖREBRO · Eva Nordin
Reumatologkliniken vid Örebro
universitetssjukhus
Vissa kallade henne modig, andra ifrågasatte hennes omdöme då hon som
nybliven specialist tackade ja till att
bli verksamhetschef för reumatologkliniken vid Örebro universitetssjukhus.
Själv är Sara Bucher entusiastisk och väl
medveten om de utmaningar hon står
inför. Den 1-4 april är kliniken värd för
Reumadagarna i Örebro.
F
rån tågstationen är det en rak promenadväg på ungefär en kvart till sjukhusets huvudentré.
Det har gått cirka 14 år sedan det fick status
som universitetssjukhus, och sedan våren
2011 bedrivs här utbildning av läkare i nära
samarbete med Örebro universitet.
För att möta de nya kraven på forskning
och utbildning satsar Örebro läns landsting
för fullt på nya byggnationer; ett nytt Campus håller att byggas, men det är bara en del
i en större byggnadsförnyelse som syftar till
att utveckla universitetssjukhuset.
En arkitekttävling har också genomförts
och flera förslag har tävlat om uppdraget att
utforma ett nytt högspecialitetshus som ska
rymma såväl öppen som slutenvård inom
områden som ögon, öron-näsa-hals, käkkirurgi, plastikkirurgi, hud, handkirurgi och
anestesi.
– Det finns stora ambitioner från både
sjukhusledningen och landstinget. Samtidigt inser jag också att det finns flera stora
utmaningar för att klara de uppdrag som
ryms inom ett universitetssjukhus, säger
Sara Bucher.
Uppförsbackarna är många. I slutet av
januari publicerade Dagens Medicin en
rankinglista över Sveriges bästa universitetssjukhus. Örebro hamnade på näst sista
plats. I genomgången hade man tittat på
parametrar som medicinsk kvalitet, vårdgaranti, patientenkäter, ekonomi, hygien,
läget på akuten, vårdplatsläge. Man hade
också utgått från registerdata från Öppna
jämförelser, patientenkäter och mätningar
av olika slag.
– Vi behöver arbeta intensivt och målmedvetet de närmaste åren för att utvecklas till
ett fullfjädrat universitetssjukhus. Om jag
går till min egen verksamhet har Reumatologkliniken i Örebro varit en av Sveriges
största kliniker, i dag är det en av landets
minsta. Vi befinner oss också i en omfattande omorganisation, tre sjukhus ska slås
ihop i en och samma förvaltning och myck-
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et är ännu oklart kring hur den nya organisationen skall se ut. Det skapar osäkra förutsättningar för verksamheterna i det korta
perspektivet. Helt klart är att vi inte kommer slås samman med andra specialiteter
till en storklinik, säger Sara Bucher.
Från specialist till verksamhetschef
Det är måndag förmiddag på Reumatologkliniken. Sara har just kommit tillbaka efter en sportlovsvecka tillsammans med sin
familj och har just den här dagen bakjour.
Det dröjer inte länge förrän telefonen ringer och kollegor knackar på dörren för konsultation.
På skrivbordet ligger boken ”Den kommunikativa chefen- en handbok om kommunikation för chefer i Örebro läns landsting”.
På en stol vid fönstret vilar en oljemålning
som föreställer ett nyfött barn framför ett
sjukhus. Den är målad av Saras syster som
är konstvetare och arbetar med konstutsmyckningar inom vården.
– Jag är uppvuxen i en akademisk familj
med stort kulturintresse. Det har präglat
mig. Kulturen är en viktig del i den medmänskliga kommunikationen, och det finns
mycket forskning som visar den betydelsefulla roll och den läkande kraft som konsten, musiken och litteraturen har.
Det har bara gått cirka sju veckor sedan
Sara Bucher tillträdde som verksamhetschef. Hon är 38 år och blev klar specialist i
reumatologi i december förra året.
Hon gjorde sin AT i Karlskrona och sökte
sig till Örebro 2006 för att göra sin specialisttjänstgöring. Sara Bucher är född i Örebro och ville gärna arbeta på ett universitetssjukhus, men också komma tillbaka till
hemstaden. Även Saras man gillar staden,
han är utbildad planarkitekt och arbetar i
Örebro kommun. Tillsammans har de två
barn och gillar de fördelar som finns med
att bo i en mindre stad än Stockholm. Vardagslivet är lite enklare; närheten till skola
och arbete väger tungt. Varje morgon promenerar Sara till arbetet och får då en stund
för sig själv.
– Jag brukar stänga av mobilen och försöka
vara närvarande i det som är, en slags mindfulnessövning innan arbetsdagen startar.
Långsiktigt perspektiv
Kliniken har sökt ny verksamhet under ett
par års tid och i juni 2013 övergavs kravet
på att sökande skulle vara specialist i Reu-
matologi. I november stod det klart att Sara
Bucher skulle ta över chefskapet. Men det
var det inte en självklarhet att hon skulle
söka tjänsten. Hennes ursprungliga plan
var att arbeta som reumatolog några år för
att bli en duktig kliniker, gärna med en möjlighet att också forska.
– Jag satt med i klinikledningen när vi letade efter en ny verksamhetschef, men det
växte inte kandidater på träd. När kravet på
att vara specialist släpptes såg jag chansen
och möjligheterna att arbeta med målet
och visionen att utveckla Reumatologkliniken till en välfungerande universitetsklinik
med akademisk höjd och med en god arbetsmiljö.
Sara Bucher går mot strömmen. Ledarskapet i hälso- och sjukvården har länge
betraktats som en ödesfråga. Undersökningar visar att det är svårt att hitta ledare
i läkarkåren. Många läkare har valt läkaryrket för att de vill arbeta med patienter och/
eller forska, och prioriterar inte att axla ett
Sara Bucher
Sara Bucher
chefskap. På läkarutbildningen finns heller
inte mycket om ledarskap som förbereder
läkare för chefsrollen.
– Jag är genuint intresserad av ledarskapsfrågor, hur man får människor att blomma
och bli motiverade att prestera. På läkarutbildningen ansvarade jag för utbildningsfrågor, jag har också arbetat fackligt.
– Mitt förordnande är på fyra år, men jag
vill gärna stanna åtta år. Det är ett bra tidsperspektiv och det ger också en stabilitet
och tydlighet, vilket är viktigt i den situation vi befinner oss i.
Resan mot en universitetsklinik
Reumatologiska kliniken i Örebro bildades
1966. Upptagningsområdet omfattar cirka
280 000 invånare. Kliniken som ansvarar
för cirka 3 500 patienter (enstaka regionpatienter kommer från Värmland) har cirka
600 nybesök samt 2 800 återbesök per år.
Kliniken uppfyller till stor del vårdgarantin
för nybesök inom 60 dagar, men en otillfredsställande andel av återbesöken sker
inom avtalad tid.
Kliniken är i dag underdimensionerad. Läkargruppen består av sju specialister, varav
en är disputerad och en är dubbelspecialist
i företagshälsovård, samt två ST-läkare.
Enligt Svensk Reumatologisk Förenings
beräkningar skulle kliniken behöva 14 specialister för att klara sitt uppdrag. Kliniken
ställs dessutom inför ytterligare en utmaning då fyra av de sju specialisterna är över
60 år och flera står inför pension.
– En stor utmaning är att kunna säkra utbildningskvaliteten och behålla den kliniska kompetensen då flera av våra seniora och
erfarna läkare inom en snar period kommer
att sluta. Vi kommer att behöva rekrytera
nio specialister. Jag har redan nu fått löfte
om att nyanställa tre ST-läkare samt en specialist, och det är en bra början, säger Sara
Bucher.
En annan stor utmaning är att utveckla
kliniken till en välfungerande universitetsklinik. Det saknas i dag forskning vid kliniken; den höga produktionen i kombination
med underbemanning har gjort det svårt
att frigöra tid och resurser för forskning. I
dag når kliniken inte upp till kraven på en
universitetsklinik när det gäller kvalitetsarbete och medicinsk vetenskap. Frågan är
högt prioriterad, menar Sara Bucher.
– En förutsättning för att lyckas med målet är att vi kan rekrytera flera läkare. Mina
specialistläkare ansvarar för cirka 550 patienter, många fler än riksgenomsnittet.
– Vi har just påbörjat resan mot att bli en
riktig universitetsklinik med en kreativ
forskningsmiljö och en vetenskaplig produktion. På sikt ser jag det som naturligt att
klinik och forskning går hand i hand. Vi försöker nu identifiera viktiga forskningsområden och söker samarbeten med Örebro
universitet för att skapa broar mellan klinik
och akademi.
Klinisk inflammationsforskning är ett prioriterat område för sjukhuset och finns i
dag vid ett flertal kliniker inom exempelvis medicin, infektion, kardiologi, hud och
urologi. På universitetssidan finns etablerad immunologisk forskning med fokus på
inflammationsforskning. Sara Bucher vill
gärna skapa ett brett forskningsnätverk av
kliniker och institutioner där reumatologi
är en viktig del av det framtida forskningssamarbetet.
Sara Bucher inser att det kommer att krävas
en stor målmedvetenhet, men också prestigelöshet. Det är många frågor och områden hon måste erövra, såväl inom sin egen
organisation som inom landstinget.
– Jag är relativt ung, nyfiken och analytiskt
lagd. Men jag har ingen lång erfarenhet
av varken klinisk reumatologi eller forskning. För mig handlar det om att vara nyfiken, men också om att våga be om hjälp.
Jag har tillgång till en fantastisk mentor i
min egen organisation, jag har också stöd i
Svensk Reumatologisk Förening, som jag är
en del av. Sedan finns det en starkt uttalad
ambition i landstinget att man ska satsa på
forskning.
En tredje utmaning är att leverera bra beslutsunderlag till politiker och tjänstemän
så att vården kan utvecklas på ett kvalitets-
säkert sätt utifrån patienters behov.
Landstinget i Örebro har tydligt markerat
att de vill ta avstånd från New Public Management och i mycket större utsträckning
satsa på kvalitetsindikatorer och värdebaserade ersättningar, menar Sara Bucher.
– Det finns en bra viljeinriktning. Vi ligger bra till i Öppna jämförelser, men när
det gäller nationella riktlinjer för rörelseorganens sjukdomar så återstår en hel del
att göra vad gäller implementering. Jag ser
riktlinjerna som ett bra verktyg och en möjlighet att uppnå de mål som tydligt finns
uttryckta i riktlinjerna.
Vill vara ett föredöme för yngre
Trots ett tungt ansvar som verksamhetschef, har Sara Bucher varit mån om att få
fortsätta arbeta kliniskt. Hon ansvarar för
cirka 250 patienter och har mottagning ungefär en vecka i månaden. Var sjätte vecka
är hon bakjour.
Det är fantastiskt, menar hon, att arbeta
inom en specialitet där landvinningarna
inom forskning och behandling närmast
kan betraktas som revolutionerande. Sara
beskriver reumatologi som en intellektuell
specialitet med stor humanism. Hon hoppas att hon som verksamhetschef ska kunna
vara ett föredöme för yngre läkarstuderande och även inspirera fler att välja specialiteten.
– Det finns fortfarande gamla föreställningar om att man som reumatolog jobbar
med äldre och besvärliga människor som
har ont.
Men jag brukar säga att man får möjligheten att arbeta som Dr House. Man ställs
ofta inför kliniskt knepiga frågeställningar
som kräver breda och omfattande kunskaper, men också kreativitet och analytisk
förmåga.
Om några veckor står Reumatologiska kliniken som värd för Reumadagarna i Örebro.
Även i år kommer Svenskt Reumaforum, Föreningen Reumasjuksköterskor samt Reumatikerförbundet att vara medarrangörer
och hålla i ett eget program med fokus på
patient, omvårdnad och rehabilitering.
Vid sidan av det vetenskapliga programmet, kommer även ett symposium om pedagogik att hållas: ”Dagens pedagogiska
utmaning: Allt ljus på den informerade patienten och den självständiga studenten?”.
– Örebro universitet har en mycket dynamisk och modern syn på pedagogik. Vi är
mycket aktiva att bygga och utveckla den
verksamhetsförlagda delen av läkarutbildningen, och är av åsikten att det behövs mer
fokus på pedagogik under läkarutbildningen. Till exempel är utbildning inom teamet,
inklusive patienten, särskilt viktigt inom
reumatologin.
Därför arrangerar vi ett symposium med
pedagogik, säger Sara Bucher.
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Fakta
Reumatologkliniken vid Örebro universitetssjukhus
Anställda
Kliniken har 27 anställda varav 7 specialistläkare, samt 2 STläkare.
Upptagningsområde
Cirka 280 000 invånare. Enstaka regionpatienter kommer
från Värmland (myosit och systemisk skleros samt enstaka
second opinion).
Slutenvård
Bedrivs med fem platser för medicinsk utredning (varav två
är sju-dygnsvård) samt tre för slutenvårdsrehabilitering och
två som behandlingsplatser.
Vid kliniken finns även dagvårdsrehabilitering. Varje vecka
ges cirka drygt 40 infusionsbehandlingar.
Poliklinisk verksamhet
Vid mottagningen görs varje år cirka 3 500 läkarbesök, 800
sjuksköterskebesök samt 1300 besök till arbetsterapeuter
och kuratorer. Här finns flera specialmottagningar och tidig artrit-mottagning. Det saknas i dagsläget en självständig
sjuksköterskemottagning.
Beredskap
Verksamheten innehåller reumatologjour och beredskap
dag- och kvällstid för specialister. Här finns även konsultverksamhet och telefonrådgivning. Mot slutet av specialisttjänstgöringen deltar de även i konsultverksamhet. Klinikens
läkare deltar i medicinklinikens jourverksamhet med ett
dag/kvällspass var tredje vecka.
Kvalitetsgranskade
Kliniken har genomgått flera SPUR-inspektioner, 1998 och
2007. I februari 2014 genomfördes den senaste inspektionen,
rapporten är i skrivande stund inte publicerad.
I Örebro bygger man för fullt. Ett nytt högspecialitetshus ska byggas och en arkitekttävling har utlysts. Här är en del av ett
av förslagen från Centrum för vårdens arkitektur på Chalmers.
Koordinator sökes
till Svensk Reumatologisk Förenings kansli
Svensk Reumatologisk Förening (SRF) söker en koordinator på heltidstjänst
till vårt kansli med arbetsplatser både vid Reumatologkliniken Karolinska
Universitetssjukhuset Solna och QRC (Kvalitetsregistercentrum) Solna. Din
funktion blir att vara en kombination av kanslichef, administratör, projektledare och verksamhetsutvecklare.
• Ge administrativt stöd till/föra protokoll för SRF styrelse, dess Registerråd
samt arbetsgruppen ARTIS (Anti-Reumatisk Terapi I Sverige)
• Sprida och popularisera resultat från forsknings- och utvecklingsarbete
• Ansvara för dokumenthanteringssystem
Du bör vara utåtriktad, service-minded, initiativrik, ha administrativ kompetens
och vana av självständigt arbete. Mycket god samarbetsförmåga är ett krav. Forskningskompetens liksom tidigare erfarenhet av registerarbete är meriterande.
Din ansökan skickas till SRF-ordförande Ralph Nisell
([email protected]), senast den 27 mars.
Huvudsakliga arbetsuppgifter:
• Vara kontaktperson för medlemmar, SRQ
(Svensk Reumatologis Kvalitetsregister), företag och vid uppdragsforskning
• Ansvara för utveckling och förbättring av hemsida och andra kontaktytor
• Organisera och administrera SRFs nationella möten 1-2 gånger per år
6
Din arbetsgivare blir ”SRF Service AB”.
Förutom CV skriv även ett kort personligt brev där det framkommer varför just
du söker denna tjänst. Stor vikt läggs vid personlig lämplighet.
Tillträde enligt överenskommelse.
Intervju med Maria Berglund
Maria Berglund är ST-läkare i reumatologi och har haft en tjänst på kliniken i
ett år. Hon tog sin läkarexamen i Danmark och gjorde sin AT i Örebro. Under
den valfria klinikplaceringen valde hon
Reumatologkliniken. Och där han hon
stannat.
S
pecialiteten är spännande på många
sätt tycker hon.
– Jag gillar den delen som handlar
om att utforska och vara nyfiken, det krävs
en slags Sherlock Holmes förmåga för att
bli en duktig kliniker, och det gillar jag. Det
är också en specialitet där samspelet mellan läkare och patient är väldigt viktigt. Det
finns i dag omfattande behandlingar, samti-
digt är flera av dem förknippade med svåra
biverkningar. Det gäller att vara lyhörd för
patientens behov och sätta sig in i patientens perspektiv och de förväntningar som
finns på behandlingsresultat.
Hur ser du på kliniken idag och de möjligheter som finns för framtiden?
– Jag kom till kliniken i ett läge då flera
av de seniora specialisterna var på väg mot
pensionsålder. Nu finns det än så länge
resurser för att klara utbildningsbehovet,
men fler läkare måste rekryteras och det är
så klart ett orosmoment.
Vilka styrkor ser du hos Sara Bucher?
– Hon är driven och entusiastisk och har
ett stort stöd hos vårdpersonalen. Jag upplever Sara som ambitiös, engagerad och lyhörd. Hon drivs av en stark vilja att skapa
förändring och vidta förbättringsåtgärder.
Det känns tryggt. Jag tror att hon kan åstadkomma något väldigt bra.
I dag bedrivs ingen forskning vid kliniken, skulle du själv vilja forska om möjligheten fanns?
– Sara försöker driva kliniken mot forskning och utveckling och det är väldigt bra.
I dag är jag inte i så mycket kontakt med
forskning, men det finns en önskan hos mig
att det på sikt ska kunna ingå i min tjänst.
Förutsättningen är dock att vi blir fler, i dag
har vi en alltför hög arbetsbelastning för att
också kunna klara av forskning.
Hur vill du beskriva stämningen på kliniken?
– Den är väldigt familjär. Det finns en
stark positiv känsla på kliniken. Det är korta beslutsvägar och det finns en anda av
att ”ingenting är omöjligt”. Vi arbetar nära
varandra, på både mottagningen och vårdavdelningen. Det är högt i tak att pröva olika saker, diskutera och omvärdera och det
värdesätter jag mycket.
Maria Berglund
7
SRF´s STYRELSE 2014
Ralph Nisell
Ordförande
Reumatologiska Kliniken
Karolinska Universitetssjukhuset
171 76 Stockholm
Tel 08-517 760 93
[email protected]
Utrota
barncancer.
Boel Mörck
Vice ordförande
Reumatologiska kliniken
SU/Sahlgrenska
413 45 Göteborg
Tel 031-342 10 00
[email protected]
Din gåva gör skillnad.
Gerd-Marie Alenius
Facklig sekreterare
Reumatologiska Kliniken Västerbotten
Norrlands Universitetssjukhus
901 85 Umeå
Tel: 090-785 16 76
[email protected]
Britt-Marie Nyhäll-Wåhlin
Kassör
Kliniken för reumatologi
Falu lasarett
791 82 Falun
Tel 023-49 27 22
[email protected]
Vetenskaplig sekreterare
Universitetsöverläkare
IKE, avd f Reumatologi,
Hälsouniversitetet
581 85 Linköping
Tel: 010-1032416
[email protected]
Ann Knight
Utbildningsansvarig
Verksamhetsområde Reumatologi
Verksamhetsområde Hudoch Könssjukdomar
Akademiska Sjukhuset
751 85 Uppsala
Tel 018-611 92 29
[email protected]
Yulia Stennikova
Ledamot, representant för
läkare under utbildning
Östersunds sjukhus
Östersunds rehabcentrum
Remonthagen
Reumatologmottagningen
831 83 Östersund
Tel: 063-153000
[email protected]
6
BCF_plugg_115x297.indd ReumaBulletinen
3
Nr 96 · 2/2014
2013-04-26 10:33
Intervju med Awat Jalal
Awat Jalal tog sin läkarexamen i Irak.
Han gjorde sin AT och ST i Norrköping
och har en dubbelspecialistexamen i internmedicin och reumatologi.
H
an är överläkare och har arbetat
på Reumatologiska kliniken i över
20 år. Då han började var kliniken
välfungerande med god klinisk verksamhet
och hade en god bemanning med erkänt
duktiga kliniker.
Hur ser du på kliniken idag och de möjligheter som finns för framtiden?
– Vi har en självständig klinik med duktig
och trevlig personal. Jag trivs bra på kliniken. Det är olyckligt att antalet läkare minskat under många år. Samtidigt växer vårt
uppdrag, då har det tillkommit potenta antireumatiska mediciner som kräver läkarinsatser. Jag skulle nog säga att vi inte hunnit tillräckligt långt med vårt uppdrag. I
dag klarar vi till exempel inte av att erbjuda
våra patienter rimliga återbesökstider. Som
läkare kan jag ofta känna mig otillräcklig
och detta har konsekvenser för patienterna.
Vi har fått en ny verksamhetschef och jag
tror att det finns goda förutsättningar att vi
ska kunna bli fler specialister, och då får vi
också större möjligheter och mer tid att satsa på forskning och utveckling.
Vilka styrkor ser du hos Sara Bucher?
– Hon tillsattes på ett demokratiskt sätt.
Samtliga fackföreningar har varit med i
chefsrekryteringsprocessen och vi föreslog
henne till sjukhusledningen. Sara Bucher
har klara ledarförmågor, hon är tydlig och
ärlig som person. Den mest akuta åtgärden
är att rekrytera fler läkare. I dag har vi två
läkare som redan har fyllt 65 år, och två seniora läkare som inom kort ska gå i pension.
De ska ensam klara ett stort utbildningsbehov. Jag har stort förtroende för henne och
att hon tillsammans med klinikens anställda ska klara de problem och utmaningar
som vi brottas med.
EVA NORDIN
Awat Jalal
Hjälp oss att rädda dig.
Vi är en ideell förening utan bidrag från staten. Ditt stöd behövs för att vi ska kunna rädda liv till sjöss.
Ge ett bidrag eller bli medlem på sjoraddning.se. Du kan också ringa 077-579 00 90.
Dina pengar kommer fram! Vi har 90-konto och kontrolleras av Svensk Insamlingskontroll.
9
MÖTESPROGRAM · Reumadagarna i Örebro
Mötesprogram
Time
Tisdag 1 april
10:00-12:00 Tid för Grupper
12:00-13:00Registrering/Lunch
13:00-13:10Introduktion
13:10-14:10Introföreläsning
Konsten att njuta av kemi
Lokal: Hjalmar Bergman
Ulf Ellervik
Bengt Wahlin: Prediction of coronary artery calcification and relation to inflammation in rheumatoid arthritis: A fol-
low-up study.
Mitra Nadali: Transcriptional
activity of adipose tissue may be an early marker of cardio-
vascular risk in rheumatoid arthritis.
Anders Bengtsson: Type I interferon-mediated decrease
of serotonin synthesis in sys-
temic lupus erythematosus – a possible relation to cardio-
vascular disease?
Anna Ighe: Application of the
2012 Systemic Lupus Internanational Collaborating Clinics
Classification criteria on a regional Swedish systemic lupus
erythematosus register.
Nanna Svartz-föreläsning 2013
Carol Langford, Cleveland
Clinic, OH,
Moderator: Anna Rudin
Anna Tjärnlund: Progress report on the development of
new classification criteria for adult and juvenile idiopathic inflammatory myopathies.
17:00-18:00 Nanna Svartz-föreläsning 2014
teatern. Betty Diamond,
Manhasset, NY
Moderator: Christopher Sjöwall
18:00
Time
Mingelkväll, konferenscentrum
Lennart Jacobsson: Patients witn non-AS axial SPA and AS
have similar prevalence and levels of patient reported out
comes measures. Results from
a population based study.
10:00-12:00 Postervandring abstracts/ fika
08:30-
Utvalda abstract inom
reumatologisk forskning
Moderator: Agneta Zickert, Björn Löfström
14:10-14:30Kaffe/Te
14:30-16:00Värdarrangörssymposium
Dagens pedagogiska utma-
ning: Allt ljus på den infor-
merade patienten och den självständiga studenten?
Moderator: Marie Vallgårda
Marie Lidskog, Helen Setterud
Elisabet Welin Henriksson
Ulrika Bergsten
16:00-17:00
Onsdag 2 april
12:00-13:00Lunch
13:00-13:30 Pris och föredrag bästa
abstracts
10:00
Pauline Raaschou: TNF in-
hibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis – a nationwide cohort
study.
13:30-14:15 Utdelning och föredrag
Pfizers stora forskningsstipendium
15:00-16:30
10
Lotta Ljung: Good response on tumour necrosis factor inhibitors are associated with
a decreased risk of acute coronary syndromes in patients with rheumatoid arthritis.
14:15-15:00Kaffe/Te
Speakers corner företag
Axplock avhandlingar
Niklas Hagberg, Uppsala
Kristofer Andréasson, Lund
Karin Hellgren, Stockholm
Annelie Bilberg, Göteborg
Emma Haglund, Lund
16:30-17:30 SRF föreningsmöte
19:00
Vårmötesmiddag St. Hotellet
Time
Torsdag 3 april
08:30-10:00Temasymposium
Tyrosinkinas-hämmare
Moderator: Anna Rudin
Catharina Lindholm
Ronald van Vollenhoven
Johan Richter
10:00-10:30Kaffe/Te
10:30-12:00
Temasymposium PMR/TA
Moderator: Ann Knight
Elisabeth Nordborg
Johan Fredén-Lindqvist,
Augustinas Sakinis
Carl Turesson
12:00-13:00Lunch
13:00-14:30Temasymposium
Behandling vid SLE
Moderator:
Iva Gunnarsson
Ioannis Parodis
Anders Bengtsson
14:30-15:00Kaffe/Te
15:00-16:00
Utdelning och föredrag
Pfizers stipendium för yngre
forskare 2013 & 2014, Pfizers stipendium för samarbets-
projekt, MSD Reumatologi stipendium samt Abbvies sti-
pendium för yngre forskare
16:00-18:00 Tid för grupper
18:00
Guidning och middag
Örebro slott
Time
Fredag 4 april
08:30-09:30 Interaktiva seminarier:
Hyper IgG4-syndrom - i teori
och praktik
Moderator: Lilian Vasaitis Interaktiva seminarier:
SLE - finns det en ”modern” behandling?
Moderator: Lars Rönnblom
09:30-09:50Kaffe/Te
MÖTESPROGRAM · Reumadagarna i Örebro
09:50-10:50 Interaktiva seminarier
Nya biologiska terapier
vad kan vi vänta oss?
Moderator: Ronald van
Vollenhoven
Interaktiva seminarier
Rituximab vid behandling av systemiska vaskuliter
Moderator: Per Eriksson
10:50-11:00 Nästa punkt startar 11:00
11:00-12:00 Biosimilarer - vad är det och
hur ska vi hantera dem?
Helena Møllby, Ann Johnsson
12:00-12:30 Summering av mötet
Värdarrangör
12:30-13:30Lunch
13:30-15:30 Studiebesök lokal klinik
Parallellt program SveReFo, FRS, RF
Time
Onsdag 2 april
12:00-13:00Lunch
Mathilda Björk,
Petra Wagman
09:30-10:00 Kost vid reumatisk sjukdom
Ann-Charlotte Elkan
10:00-10:30Kaffe/Te
10:30-11:00 Rök-avvänjning inom
reumatologi
Marie-Louise Karlsson
11:00-12:00 Avslutning arrangörerna
12:00-12:15 Avslutning arrangörerna
12:15-13:00Lunch
Hitta till Conventum
Olof Palmes Torg 1 · 702 22 Örebro, Sverige
Med tåg
Centralstationen ligger centralt och många av tågen stannar till vid Örebro Södra, en liten station
som ligger endast tvåhundra meter från Conventum!
Med bil
WGS 84 (lat, lon): N 59° 16.098’, E 15° 12.490’
WGS 84 decimal (lat, lon): 59.26830, 15.20817
RT90: 6572079, 1465955
SWEREF99: 6569946, 511867
Med flyg
Örebro har dagliga direktförbindelser med
Malmö/Sturup och Köpenhamn/Kastrup.
13:00-13:30 Välkommen- arrangörerna
Icke-farmakologiska åtgärder
vid reumatisk sjukdom – vad säger Socialstyrelsens
riktlinjer? Christina Opava
13:30-14:15Levnadsvanor
Matthias Lidin
14:15-15:00Kaffe/Te
15:00-16:00Avhandlingar
Personcentrerad vård i reu-
matologisk omvårdnad
Ingrid Larsson
16:30-18:00 SveReFo, FRS föreningsmöte
19:00Vårmötesmiddag
Stora Hotellet
Parallellt program SveReFo, FRS, RF
Time
Torsdag 3 april
08:30-09:30 Balans och viktiga
aktiviteter i vardagen
11
12
Folkets Hus, stockholm / 20–23 september 2014
Scandinavian Congress of Rheumatology
Den 35:e Skandinaviska kongressen i reumatologi
20–23 sept 2014 i Stockholm
Välkomna till den 35:e Skandinaviska kongressen i reumatologi som kommer att äga rum den 2023 september, 2014 i Folkets hus, City konferenscenter vid Norra Bantorget i centrala Stockholm.
Som vi tidigare har meddelat kommer den skandinaviska kongressen 2014 att ha ett fokus på områden som
är av gemensamt intresse i de skandinaviska länderna. Ett viktigt mål med kongressen 2014 är att ge unga
forskare som arbetar med vetenskap inom reumatologi möjlighet att presentera sig och sin forskning. Ett
annat viktigt mål är att lyfta fram tvärprofessionell forskning inom Skandinavien. Kongressen sker i samarrangemang mellan Scandinavian Society for Rheumatology, Svensk Reumatologisk Förening, Nordiskt
Reumaråd som representerar de nordiska patientföreningarna, nordiska Health Professionals och barnläkare
från Skandinavien.
Det är nu möjligt att börja lägga in abstracts. Sista dagen att skicka in abstrakt är den 15 april, 2014.
Nedan följer de områden som kommer att finnas med på programmet som vetenskapliga sessioner:
•
•
•
•
•
•
•
•
•
•
•
•
•
How to apply current knowledge comparing the effectiveness of
treatments for rheumatic diseases
Treatment strategies for RA- Today and tomorrow
The pre-clinical and very early phases of RA: disease mechanisms and
opportunities for prevention
Pain in rheumatic diseases- clinical and molecular aspects
Spondyloarthritis (ankylosing spondylitis and psoriatic arthritis)
with modern management of psoriatic arthritis and ankylosing spondylitis
Modern imaging – clinical and molecular
Osteoarthritis – Molecular and Clinical aspects
Fatigue and cognitive dysfunction in rheumatic diseases
Life style factors and intervention in rheumatic diseases
Modern anti-rheumatic treatment and current strategies for prevention of infections
Immunological mechanisms and clinical phenotypes in inflammatory systemic diseases
Autoinflammatory diseases
Adolescent rheumatology
Därutöver kommer vi att ha workshops kring olika teman och några s.k. keynote lectures, varav en om
ANCA–associerad vaskulit, där professor David Jayne från Cambridge har tackat ja.
Följ utvecklingen av programmet på www.scr2014.se
Varmt välkomna!
Ingrid LundbergRalph Nisell
Scandinavian Society for RheumatologySvensk Reumatologisk Förening
13
ABSTRACTS
Reumadagarna 2014 - Abstracts
Premiärdags! Välkommen till Reumadagarna i Örebro! I år är det premiär för vår nya mötesordning. Därför är det fantastiskt
roligt att kunna konstatera att den vetenskapliga aktiviteten är fortsatt hög inom svensk reumatologi. De vetenskapliga
bidragen har aldrig varit fler än i år (jämfört med tidigare Riksstämmor). Hela 95 stycken abstractbidrag har inkommit och
accepterats för presentation under Reumadagarna. 83 av dessa inkom till SRF och har kvalitetsgranskats av SRFs professorskollegium, medan 12 granskats av FRS/SveReFo.
Posters kommer att hänga uppe i Conventums foajé under hela onsdagen den 2 april. Mellan kl 10-12 kommer författarna
finnas vid sina respektive posters. 8 bidrag har av SRFs professorskollegium utvalts för muntlig presentation, dessa framförs
på morgonen samma dag i sal Tunnbindaren med start 08:30.
På följande sidor finner Ni samtliga abstractbidrag. För några av bidragen visas endast titel, författare och hemvist. Detta är
inte något redaktionellt misstag utan svarar mot ett önskemål från flera av forskarna. Genom att bidragen inte publiceras i
sin helhet finns inga formella hinder för att de presenteras vid internationella möten som tidsmässigt ligger efter Reumadagarna. På detta sätt kan vi bjudas på nyheter innan de når större reumatologikretsar på t.ex. Eular eller ACR.
Än en gång, varmt välkomna!
Christopher Sjöwall, Vetenskaplig sekreterare
ABSTRACTNUMMER: 1
1
Kvalitetsregister med kvalitet
Lotta Ljung1,2, Johan Askling1
Institutionen för medicin, enheten för klinisk epidemiologi, Karolinska Institutet, Stockholm 2 Institutionen för folkhälsa och klinisk
medicin/Reumatologi, Umeå Universitet, Umeå
sponsdata ökade med i genomsnitt 14/år, men minskade procentuellt från 86 % 1999 till 62 % 2010. Individer som startade med ett
icke-anti-TNF-preparat (5 %) hade tillgängliga EULAR-responsdata i lägre utsträckning (55 % jämfört med 71 % för anti-TNF),
vilket endast delvis förklaras av en lägre registreringsgrad under
senare år.
1
Täckningsgraden i Svensk Reumatologis Kvalitetsregister (SRQ)
för förskriven TNF-hämmarbehandling vid reumatoid artrit (RA)
har beräknats vara omkring 90 %. Syftet med denna undersökning
var att ge en överblick över tillgängliga uppföljningsdata i registret.
Metod
Individer (n=19631) som påbörjat ett första biologiskt läkemedel 1999-2010 identifierades i SRQ. Vid RA-diagnos beräknades
andelen där registreringen möjliggjorde beräkning av EULAR- respons (samtliga DAS 28-variabler registrerade vid start och vid
besök efter 2-12 månader). Vid psoriasisartrit (PsoA), spondartrit
(SpA) eller ankyloserande spondylit (AS) beräknades andelen med
minst en aktivitetsvariabel (SR, 28-ledstatus, global VAS, läkarbedömning, DAS28 och/eller BASDAI) från behandlingsstart och vid
uppföljning efter 2-12 månader.
Konklusion
Besöksregistreringarna i SRQ för patienter med en första bio-behandling håller en hög kvalitet.
Bortfallet avseende uppföljningsdata förklaras delvis av avslutade
behandlingar men huvudsakligen av ofullständiga registreringar
eller saknade/oregistrerade besök. Om SRQ ska kunna användas
för uppföljning av behandlingseffekt bör registreringsfrekvensen
bibehållas på en hög nivå.
ABSTRACTNUMMER: 2
2
Hur stor andel av alla patienter med reumatoidartrit som behandlas med biologiska eller ickebiologiska dmards idag täcks av SRQ?
Kristin Waldenlind2, Hjalmar Wadström1, Martin Neovius1, Johan Askling1,2
Enheten för klinisk epidemiologi, Institutionen för medicin, Karolinska Institutet, Stockholm 2 Enheten för reumatologi, Institutionen för
medicin, Karolinska Institutet, Stockholm
1
Resultat
För individer med RA-diagnos (n=12037) fanns totalt 34649 registrerade besök under året efter behandlingsstart, varav 88 % med samtliga DAS28-variabler. Vid PsoA (n=2306) och AS (n=1485)/SpA
(n=1305) noterades 6152 respektive 6986 besök, med minst en
aktivitetsvariabel registrerad i nära 100 % av besöken.
BASDAI-registrering vid SpA/AS ökade från 1 % 2004 till 40 %
av besöken 2010. EULAR-responsdata vid RA fanns för 69 % och
aktivitetsdata vid start och uppföljning vid PsoA och AS/SpA för 78
respektive 74 % av individerna. I 10-13 % hade behandlingen avslutats och data saknades. Registrering saknades eller var ofullständig
för 12-18 %. Antalet individer med RA och tillgängliga EULAR-re-
14
Bakgrund
Svensk reumatologis kvalitetsregister (SRQ) är unikt och har gett
upphov till flertalet studier för främst biobehandlade patienter med
reumatoid artrit (RA), där täckningsgraden har beräknats till
87%, medan täckningsgradsiffror för totala patientgruppen med
RA har redovisats i öppna jämförelser. Här påvisas möjligheter och
utmaningar med täckningsgradsberäkningar för patienter med RA
i SRQ.
ABSTRACTS
Material och metod
Via patientregistret och läkemedelsregistret definierades prevalent
RA med aktiv anti-reumatisk behandling: individer ≥18 år, bosatta i Sverige 2012-12-31, ≥2 besök med RA-diagnos i öppenvårdsregistret varav ≥1 besök vid reumatologi/intern-medicinsk
avdelning, och ≥1 uthämtning av DMARD under 2012. Individer
som även haft diagnos AS/PsA/SpA/JIA exkluderades.
Registeridentifierad incident RA definierades som individer ≥18
år med ett återbesök med RA-diagnos inom 1 år efter det första besöket, varav ≥1 besök vid reumatologi/internmedicinsk avdelning,
samt ≥1 uthämtning av DMARD under 2012. Patienter med
diagnoserna AS/PsA/SpA/JIA, samt patienter med uthämtning av
DMARD >6 månader före det första besöket med RA, exkluderades. För vardera av dessa två patientgrupper (nämnarna), identifierades de som också fanns i SRQ (täljaren).
Resultat
26,058 prevalenta DMARD-behandlade patienter (prevalens=
0.34%) identifierades från patientregistret under 2012, av vilka
19,501 (75%) var inkluderade i SRQ. Högst täckningsgrad (>90%)
hade Dalarna, Östergötland, Gävleborg och Gotland, medan Västernorrland, Jönköping och Kronoberg hade de lägsta (<50%).
Stockholm och Västra Götaland hade liknande täckningsgrad
(≈80%), medan Skåne hade 60%. För incident DMARD-behandlad
RA identifierades 2043 patienter (27 per 100,000) under 2011, varav 1507 var inkluderade i SRQ (74%), med en liknande variation
för täckningsgrad över landsting som för prevalenta patienter.
Patientregistret har använts med antagandet att alla patienter med
diagnosen RA är korrekt, dock visar en preliminär valideringsstudie att 10% är felaktiga, vilket innebär att våra beräkningar bör ge
en motsvarande underskattning av den sanna täckningsgraden.
Slutsats
Av aktivt behandlade prevalenta och incidenta patienter med RA,
är minst tre fjärdedelar inkluderade i SRQ.
ABSTRACTNUMMER: 3
3
Validitet av RA serostatus i
Patientregistret och SRQ
Thomas Frisell1, Karin Hellgren1,2,
Camilla Bengtsson3, Johan Askling1,2
Enheten för Klinisk epidemiologi, Inst för Medicin, Solna, Karolinska Institutet 2 Reumatologienheten, Inst för Medicin, Solna, Karolinska Institutet 3 Institutet för Miljömedicin, Karolinska Institutet
1
Bakgrund
Det finns ett ökande intresse för forskning som studerar likheter
och skillnader mellan seropositiv och seronegativ RA avseende
etiologiska faktorer, prognostiska markörer och behandlingssvar.
Det är därför viktigt att bedöma i vilken utsträckning vi i storskaliga registerstudier kan särskilja dessa underformer från varandra.
Material och metod
Samtliga individer diagnosticerade med RA i det svenska Patientregistret (från 2001) länkades till diagnoser och reumatoid faktor (RF) i SRQ, samt till RF och antikroppar mot
citrullinerade peptider (ACPA) uppmätt i fall-kontrollstudien EIRA. Serostatus kodades från patientregistrets diagnoser med två metoder. A: Patienten tilldelades den serostatus av vilken den fått flest diagnoser; B: Vi krävde 2+ diagnoser, varav minst
en hos specialist i reumatologi eller internmedicin. Om patienten
då uppfyllde kriterier för både seropositiv och seronegativ RA an-
sågs den seropositiv. I EIRA mättes RF med nefelometri och ACPA
med anti-CCP2 ELISA.
Resultat
Med metod A/B kunde 69151/60991 individer från Patientregistret
kategoriseras som seropositiv eller seronegativ RA. Av de som även
fanns i SRQ klassificerade metod A 89% korrekt som RF-positiva,
jämfört med 82% för metod B. Motsvarande siffror för RFnegativa
RA var 94% respektive 93%. RF-status i SRQ och i EIRA stämde
överens till mer än 95%. RF-status och diagnos i SRQ stämde överens till 96%. För de som var RF-positiva enligt metod A/B och även
fanns i EIRA var 83%/77% också ACPA-positiva, medan RF-negativa oftast var ACPA-negativa (80%/84%).
Slutsats
Metod A kunde klassificera fler patienter, och visade något bättre
prediktivt värde än Metod B. Diagnos i SRQ överensstämmer väl
med RF-status i såväl SRQ som i EIRA. RF och ACPA är tydligt korrelerade, men cirka 25 % av RF-negativa är ACPA-positiva och vice
versa. Det är möjligt att göra en relativt korrekt klassificering av
RF-status baserad på RA diagnos i Patientregistret, men om möjligt
bör man använda information från SRQ och/eller kompletterande
analyser.
4
ABSTRACTNUMMER: 4
En gemensam biobanksmodul kopplad till svensk
reumatologisk valitetsregister
Thomas Bergman1, Eva Baecklund4,5, Inger Gjertsson4,6, Solbritt
Rantapää Dahlqvist2,4, Thomas Skogh4,7, Carl Turesson4,8, Johan Askling3,4
Karolinska Institutet, enheten för reumatologi, inst. för medicin 2
Norrlands Universitetssjukhhus, reumatologiska kliniken 3 Karolinska Universitetssjukhuset, reumatologiska kliniken 4 SRF arbetsgrupp för biobanker 5 Akademiska sjukhuset Uppsala, reumatologmottagningen 6 Sahlgrenska Universitetssjukhuset, reumatologiska
kliniken 7 Linköpings Universitetssjukhus, reumatologiska kliniken 8
Skånes Universitetssjukhus, reumatologiska kliniken
1
Bakgrund
Individualiserad terapi vid RA kräver kunskap om prediktorer för
respons på behandling, liksom prediktorer för bieffekter av behandling. För att möjliggöra detta krävs därför inte bara tillgång
till data från SRQ (tex respons) och eventuellt från andra register
(tex bieffekter) utan också tillgång till information om serologiska
och genetiska markörer. Vi tror därför att utvecklingen av kliniska behandlingsriktlinjer, och vår förståelse för sjukdomsprogress
och förlopp vid RA, avsevärt kan förbättras genom att systematiskt
samla in inte bara kliniska data utan även biobanksprov som möjliggör analys av genetik och serologi på våra patienter. Vårt syfte
har därför varit att skapa en enkel, transparent, robust, och kostnadseffektiv storskalig biobanksmodul kopplad till svensk reumatologis kvalitetsregister (SRQ).
Metoder
De primära inklusionskriterierna i SRQ biobank är patienter
som nyligen har insjuknat i RA och därför inkluderas i SRQ, samt
befintliga RA patienter i SRQ vilka startat biologisk behandling efter 1 januari 2010. För att underlätta rekryteringen av patienter till
biobanken har vi implementerat ett beslutsstöd, integrerat i SRQ,
som påminner om att patienten kan tillfrågas att lämna fyra blodprov. Proven (två EDTA plasma rör, ett serumrör och ett helblodsrör för DNA extraktion) skickas till BBMRI.se biobank för bered-
15
ABSTRACTS
ning och långtidsförvaring i frysar.
Resultat
Reumatologkliniken på Karolinska Universitetssjukhuset påbörjade insamling av biobanksprov under senvåren 2013.
Därefter har de åtta följande reumatologiska klinikerna och
enheterna anslutit sig och samlar in prov till biobanken; Sahlgrenska, Eskilstuna, Farsta Lars Kanerud, Falun, Danderyds
sjukhus, Kalmar, Karlskrona/Karlshamn och Akademiska sjukhuset Uppsala. Flera ytterligare kliniker planerar och förbereder biobanking via denna modul. Vid årsskiftet 2013/14 hade totalt 536 patienter lämnat prov via SRQ biobanksmodul. Med nuvarande takt
beräknas 1000 patienter ha provtagits via denna modul någon gång
under andra kvartalet 2014.
Slutsats
Arbetet med gemensam biobanksmodul har kommit igång och har
hög potential för att ytterligare förbättra utbytet av SRQ.
ABSTRACTNUMMER: 5
5
How good is the coverage and how accurate are data in
the swedish biologics register (artis)
Hjalmar Wadström, Jonas Eriksson, Martin Neovius, Johan Askling
Enheten för klinisk epidemiologi, institutionen för medicin, Solna 2
Enheten för reumatologi, institutionen för medicin, Solna
1
Background
The usefulness of biologics registers and the interpretation of results from analyses based on such data both hinge upon an understanding of the coverage of eligible patients, and on the accuracy
and validity of the data entered. Sweden with its virtually complete
national registers that can be linked together offers the possibility to compare clinical register data against a “gold standard”. The
purpose of this study was to assess the coverage of the Swedish
biologics register (ARTIS) across indications, and the accuracy of
the registered information on biologics treatment.
Methods
Through cross-reference of ARTIS national heath registers on
prescriptions (adalimumab and etanercept), outpatient visits, and
death/residency during 2008-2010, we assessed: the coverage
of ARTIS, per treatment indication, the validity of the registered
start- and stop dates, ARTIS treatments with no dispensations, and
the accuracy of the registered information on concomitant antirheumatic therapies.
Results
3945 individuals with a spondylarthropathy and 8032 patients
with rheumatoid arthritis had at least one adalimumab or etanercept prescription filled during the study period. Of these, 86% of
those with spondyloarthropathies, and 95% of patients with rheumatoid arthritis were also found in ARTIS with the corresponding
treatment. 95% of patients had filled their anti-TNF prescriptions
between the ARTIS’ start and stop dates (allowing a 90-day window). 5% of patients had their first filling of their anti-TNF prescription >60 days prior to, and 4% >60 days after, the registered
start date in ARTIS. 8% of patients had anti-TNF prescriptions filled >90 days after the registered stop date in ARTIS.
Conclusions
We observed a high coverage and accuracy of ARTIS data on biologics exposure, both for spondyloarthropathies and for rheumatoid
16
arthritis. The combination of data from clinical registers such as
ARTIS with data from national health registers offers a high quality measurement of de facto treatment.
ABSTRACTNUMMER: 6
6
The inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis - a nationwide cohort study
Pauline Raaschou1,2,3, Thomas Frisell1,2,3, Johan Askling1,2,3
Karolinska Institutet 2 Institutionen för Medicin 3 Avd. för klinisk
epidemiologi
1
Background
Tumor necrosis factor (TNF) has diverse and incompletely understood effects in tumor biology. Cancer recurrence in RA-patients
treated with TNF-inhibitors (TNFi) remains a clinically important,
yet unresolved, concern. Based on limited evidence, most clinical
guidelines advice against the use of TNFi in patients with a malignancy within five or ten years. We investigated the risk of breast
cancer recurrence in RA-patients with a history of breast cancer
starting treatment with TNFi. RA, breast cancer, and co-morbidity-related factors were taken into account.
Material and methods
Population-based matched cohort study based on prospectively
recorded data in Sweden.120 TNFi-treated (1999-2010) and 120
matched biologics-naïve individuals with RA and a history of equally recent/distant breast cancer were followed through chart reviews for breast cancer recurrence, through 2011. Hazard ratios
(HRs) for recurrence were calculated using Cox regression.
Results
The median time from breast cancer diagnosis until TNFi treatment/start of follow-up was 9.4 years. Discrete differences were
noted in breast cancer characteristics and/or treatment, at time of
breast cancer diagnosis. Mean follow-up was 4.9 years from TNFi
start (4.6 years among biologics-naïve).
Among the TNFi-treated, 9 developed a breast cancer recurrence (crude incidence rate 15/1000 person-years) during follow-up,
compared to 9 among the matched biologics-naïve (16/1000 person-years). The corresponding HR was 0.8 (95% CI 0.3-2.1). Adjusting for the observed differences in breast cancer characteristics,
the HR was 1.1 (95% CI 0.4-2.8). The HR for recurrence was similar
among patients who started TNFi within five years, and more than
five years, from their breast cancer diagnosis.
Conclusions
Among patients with RA and a history of breast cancer, those who
started TNFi treatment did not experience more breast cancer recurrences than RA patients treated otherwise. The generalizability
of our findings to women with a recent or a poor prognosis breast
cancer remains unknown.
Abstractnummer: 7
7
ARE PATIENTS WITH RHEUMATOID ARTHRITIS STILL AT AN INCREASED RISK OF TUBERCULOSIS AND WHAT IS THE ROLE OF
BIOLOGICAL TREATMENTS?
Elizabeth Arkema1, Jerker Jonsson2,3, Eva Baecklund4, Judith
Bruchfeld3, Nils Feltelius5,6, Johan Askling1,6
ABSTRACTS
Karolinska Institutet, Clinical Epidemiology Unit 2 Swedish Institute for Infectous Disease Control 3 Karolinska Institutet, Infectious
Diseases Unit 4 Uppsala University, Unit of Rheumatology 5 Medical
Products Agency 6 Karolinska Institutet, Rheumatology Unit.
1
Background
The extent to which increased awareness and pre-treatment
screening have reduced tuberculosis (TB) risk with biologicals is not clear. Our aim was to estimate the risk of TB in patients with rheumatoid arthritis (RA) both with and without
exposure to biological therapy and to directly compare the
risks between therapies.
Methods
Data from the Swedish National Population Registers, Tuberculosis Register and the Swedish Biologics Register were
used to conduct a prospective population-based national
cohort study (2002-2011). We estimated the rate of incident
TB in the general population, and in a cohort of biological-naïve and biological-exposed patients diagnosed with
RA. Cox models were used to estimate Hazard Ratios (HR)
with particular attention to risks by calendar and follow-up
time and individual biologics.
Results
Compared to the general population, RA patients not exposed to biologicals had a 4-fold increased risk of TB (HR
4.2; 95% CI 2.7 to 6.7), which did not decline over calendar
time. In contrast, the rate of TB in the biological-exposed
RA population decreased since 2002 compared to biological-naïve; from HR=8.0 (95%CI 3.4 to 18.9) in 2002-2006 to
HR=2.4 (95%CI 0.9 to 6.1) in 2007-2011. The HRs for most
recent exposure to adalimumab and infliximab compared to
etanercept were 3.1 (95%CI 0.8 to 12.5) and 2.7 (95%CI 0.7,
10.9), respectively and the HR for etanercept compared to
biological-naïve RA was 1.7 (95%CI 0.6 to 4.6).
Conclusions
In the past decade, the risk of TB has decreased among biological-exposed RA patients but remains higher than in biological-naïve RA patients. Most cases of TB in RA occur in
biological-naïve RA patients underscoring the elevated risk
also in these patients.
Abstractnummer: 8
8
IS THERE AN ASSOCIATION BETWEEN RHEUMATOID ARTHRITIS, AMYOTROPHIC LATERAL SCLEROSIS AND TUMOR NECROSIS FACTOR INHIBITOR TREATMENT?
Elizabeth Arkema, Tomas Olsson, Johan Askling
Karolinska Institutet, Institutionen för klinisk neurovetenskap 2
Karolinska Institutet, Department of Medicine, Rheumatology Unit 3
Karolinska Institutet, Clinical Epidemiology Unit
1
Background
A recent signal of an unusual number of cases of amyotrophic lateral sclerosis (ALS) was reported in patients with rheumatoid
arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi).
Our objective was to investigate this signal using a national population-based cohort study design.
Methods
Patients with RA, exposure to TNFi and ALS diagnosis were identified using national Swedish registers from 2001 to 2011. General
population comparators were selected from the national population register matched on age, sex and county to the RA population.
We calculated crude and age- and sex-standardized incidence rates
(IR) of ALS per 100,000 person-years using the overall RA population as the standard. Results Over 293,220 person-years of follow-up in the overall RA population, we observed 23 ALS cases (IR
7.8; 95%CI 5.0 to 11.8). Eighteen were TNFi-naïve and 5 were TNFi-exposed. The age- and sex-standardized IR for TNFi-naïve RA
and TNFi-exposed RA was 7.1 (95%CI 4.2 to 11.5) and 7.8 (95%CI
2.5 to 41.1) per 100,000 person-years, respectively. The standardized IR in the general population was 8.6 (95%CI 7.1 to 10.3).
Conclusion
Incidence rates of ALS were similar in the TNFi-exposed and TNFi-naïve RA populations. We found no evidence that TNFi exposure is associated with an increased risk of ALS.
9
Abstractnummer: 9
LÄKEMEDELSÖVERLEVNAD VID METOT-REXATBEHANDLING
UTAN UPPTRAPPNING
Bakgrund
Mellan 2006-2011 minskade praxis av upptrappning vid nyinsättning av metotrexat kraftigt i Falun. Vanligast blev att inleda behandling direkt med 20 mg per vecka. Syftet med studien var att
kartlägga hur detta fallit ut avseende läkemedelsöverlevnad och
sjukdomskontroll.
Material och metod
Från SRQ identifierades alla patienter som fick diagnos RA i Falun
år 2006-2011 och fick metotrexat, N=281. Vid journalgenomgång
registrerades ordinerad dos, DAS28 och ALAT vid metotrexat-start
samt vid uppföljande 3 återbesök (åb1, åb2, åb3). Orsaker till eventuell dosminskning/utsättning registrerades. Data analyserades i
JMP med ANOVA, chi-square, Wilcoxon och Tukey-KramerHSD.
Resultat
141 patienter började med 20 mg metotrexat (“20mg-gruppen”), 53
patienter fick successivt stigande dos (“Upptrappningsgruppen”),
87 patienter började med <20 mg utan att det fanns avsikt att dosöka (“Lågdosgruppen”). Frånsett att lågdosgruppen var äldre fanns
inga skillnader avseende ålder, kön, seropositivitet eller DAS28 vid
baseline mellan grupperna. Medeluppföljningstiden vid åb1 var 96
dagar utan skillnad mellan grupperna. Medeluppföljningstid vid
åb3 var 438 dagar, upptrappningsgruppen hade något kortare uppföljningstid vid åb3. 2006 inleddes 20% av metotrexatbehandlingarna med 20 mg utan upptrappning, 2011 var andelen 76%.
Behandlingar som inleddes med upptrappning minskade från 45%
till 3%. Vid åb3 var 33 metotrexatbehandlingar utsatta. Utsättning
pga biverkningar/toxicitet var signifikant vanligast i upptrappningsgruppen, N=9 (15%). Motsvarande siffra i 20mg-gruppen var
N=6 (4%) och i lågdosgruppen N=7 (8%). Utsättningsfrekvensen
var stabil över tid och påverkades inte av vilket år behandlingen inletts. DAS28 vid åb1 var i 20mg-gruppen 2,62±1,34, lågdosgruppen
3,11±1,21, upptrappningsgruppen 3,10±1,16, skillnaden var signifikant till 20mg-gruppens fördel.
Slutsats
Att inleda metotrexatbehandling med 20 mg fungerade bra när behandlande läkare bedömt detta lämpligt, denna grupp uppnådde
lägst DAS28 vid åb1. Utsättningar pga biverkningar/toxicitet var vanligast förekommande när man valt att ge metotrexat i upptrappning.
17
ABSTRACTS
Under perioden slutade man nästan helt praktisera upptrappning,
men utsättningar pga intolerans/toxicitet ökade inte. Resultaten
talar för att upptrappning inte skyddar mot utsättning pga biverkningar/toxicitet.
Abstractnummer: 10
10
PREVIOUS BIOLOGICAL THERAPIES INFLUENCE DRUG SURVIVAL IN RHEUMATOID ARTHRITIS PATIENTS STARTING ABATACEPT TREATMENT 2006-2012.
Saedis Saevarsdottir1, Leszek Stawiarz1, Carl Turesson2, Staffan
Lindblad1
1
Karolinska Institutet 2 Lund University
Background
Abatacept (Orencia®) is a biological antirheumatic drug used in
rheumatoid arthritis (RA). Our aim was to evaluate drug survival
probability of abatacept in clinical practice, using the nationwide
Swedish Rheumatology Quality registry (SRQ).
Methods
Observational data from the SRQ were collected for the period
from April 1st, 2006 to June 30th, 2012. True retention rates and
survival analysis (Kaplan Meier) with right censoring and logrank test of equality across strata were performed and Šidák multiple-comparison adjustments applied.
Results
815 RA patients (637 females, 78.2%) started abatacept between
April 2006 and June 2012 (77.5% of total 1051 patients treated with
abatacept). The median (IQR) age at start of abatacept was 61 years
(52-67) and the median duration of RA was 11.4 years (6.0-19.8). In
patients with previous biological treatment, median time since first
biological treatment to abatacept start was 3.4 years (IQR 2.4-7.9).
Median follow-up on abatacept was 0.9 years (IQR 0.4-1.9). Abatacept was prescribed as the first biological in 12.1%, after one biological drug in 26.9%, and after two or more biologicals drugs in
61%. Bio-naïve patients had significantly better drug survival than
patients with two or more previous biologicals (p=0.02). From 1 to
5 years, drug survival was respectively 72%, 55%, 49%, 49% and
49% in bio-naïve patients, 57%, 41%, 38%, 34% and 25% in those
with 1 previous biological drugs and 57%, 41%, 32%, 28% and 24%
in those with 2+ previous biologicals. A longer drug survival was
found in men compared to women (p=0.0008).
Conclusions
In this nationwide cohort of RA patients starting abatacept treatment, drug survival time was longer for bionaïve patients compared to patients previously treated with ≥2 biological drugs. Furthermore, a gender difference in favour of men was seen.
Abstractnummer: 11
11
DRUG SURVIVAL IN PATIENTS RECEIVING GOLIMUMAB TREATMENT 2010-2013. RESULTS FROM THE SWEDISH RHEUMATOLOGY QUALITY REGISTER.
Saedis Saevarsdottir1, Michele Santacatterina1, Leszek Stawiarz1, Carl Turesson2, Helena Forsblad d’Elia3, Lennart Jacobsson3, Staffan Lindblad1
1
Karolinska Institutet 2 Lund University 3 University of Gothenburg
18
Background
Golimumab (Simponi®) is a TNF inhibiting biological drug that
was approved in Sweden in 2010 for the treatment of Rheumatoid
Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis
(AS). In observational studies, the 24-month adhesion to therapy
of TNF inhibitors in bio-naïve patients has ranged from 50-70%.
The aim of the current study was to evaluate cumulative survival
probability of golimumab in clinical practice for patient with RA,
PsA, AS as well as other spondyloarthritidies (SpA).
Methods
Data were retrieved for all patients initiating golimumab treatment
from 2010 until April 30th 2013 from the nationwide Swedish
Rheumatology Quality register (SRQ). Survival analysis (Kaplan
Meier) was performed with right censoring and log-rank test of
equality across strata.
Results
Of 1681 patients initiating golimumab treatment during the study
period, 678 (40%) had RA, 364 (22%) PsA, 240 (14%) AS, 194 (12%)
SpA and 205 (12%) had other diagnoses. The proportions of women
in RA/PsA/AS/SpA patient groups were 80%/50% /28%/52%, respectively; and their median age at baseline was 58/50/45/43 years.
In patients with RA/PsA/AS/SpA, the proportions receiving golimumab as the first biological treatment were 47%/45%/41%/37%;
and the proportions receiving concurrent diseasemodifying
anti-rheumatic drugs (DMARDs) were 70%/58%/22%/38%.
When stratified by previous exposure to biological treatment (0/12/3+ biologicals), the 24-month cumulative survival probability of golimumab in patients with RA was 56%/52%/32%, PsA 56%/51%/53%,
AS 65%/57%/40% and SpA 60%/49%/47%. In RA, significant difference was observed between bio-naïve patients and those who had
previously received 1+ biological drugs (p=0.0018), a similar trend
was observed in AS patients (p=0.069), but not in PsA (p=0.6).
Conclusion
The 24-month adhesion rates to golimumab in clinical practice appear to be comparable to other TNF inhibitors, whereas further studies are necessary to evaluate the long term performance.
Abstractnummer: 12
12
DIETARY IMPACT ON METHOTREXATE IN RHEUMATOID ARTHRITIS
Cecilia Lourdudoss1, Alicja Wolk2, Camilla Bengtsson2, Lars Alfredsson2, Ronald van Vollenhoven1
1
MedS, Karolinska institutet 2 IMM, Karolinska institutet
Abstractnummer: 13
13
Tät kontroll av RA gav hög andel patienter i remisSion
Annika Teleman, Stefan Bergman
1
Axess Medica Spenshult Sjukhus 2 FoU Spenshult
Bakgrund
Täta kontroller, framför allt tidigt i sjukdomsförloppet, ger en möjlighet till förbättrad sjukdomskontroll vid RA.
Syfte
Att studera andelen patienter i remission vid 12 månader efter införandet av tät kontroll vid nydebuterad RA i vanlig klinisk praxis.
ABSTRACTS
Metod
Klinisk studie inkluderande 65 patienter med nydebuterad RA på
Spenshults reumatologiska mottagning. Läkarbesök varje månad
under det första året. Registrering i Svensk Reumatologis Kvalitetsregister (SRQ). Läkemedelsbehandlingen utifrån Svensk Reumatologisk Förenings riktlinjer. Svullna leder injicerades. Sjukdomsaktivitet bedömdes med DAS28 (≤2,6 remission, ≤3,2 lågaktiv
sjukdom och >5,1 högaktiv sjukdom).
Resultat
38 patienter kunde följas upp vid 12 månader. Förutom bortfall på
tre patienter hade övriga ännu inte uppnått 12 månaders behandling. För 95 % framgår att de uppfyller kriterier för RA (1987 och/
eller 2010). Vid inklusion var 29 % högaktiva, 49 % medelaktiva, 14
% lågaktiva och 6 % i remission. Vid 6 månader var 74 % i remission
och ytterligare 8 % lågaktiva. Vid 12 månader var 74 % i remission
och 16 % lågaktiva. DAS28 vid inklusion i medeltal 4,5 och vid 12
månader 2,0. Vid 12 månader behandlades 33 (87 %) med metotrexat varav 8 i kombination med DMARD och 3 i kombination med
biologiskt läkemedel. Tre patienter behandlades med salazopyrin
och 1 med antimalaria. 27 patienter hade prednisolon (2,5-7,5 mg).
En patient hade ingen rapporterad behandling alls.
Slutsats
Täta kontroller gav i hög grad remisson eller låg sjukdomsaktivitet
(74 resp 16 %) med ett ringa behov av biologiska läkemedel.
Patienterna förbättrades som förväntat ganska snabbt och efter 6
månader kan kontrollerna troligen glesas ut, vilket vi numera gör på
vår mottagning. Tät kontroll är en genomförbar behandlingsstrategi
i vanlig klinisk praxis och kan bidra till en ökad adherence till behandlingen och i slutänden god inflammationskontroll.
Abstractnummer: 14
14
TUMOUR NECROSIS FACTOR INHIBITORS AND THE RISK OF
ACUTE CORONARY SYNDROME IN RHEUMATOID ARTHRITIS
– A NATIONAL COHORT STUDY
Lotta Ljung1,2, Johan Askling1, Solbritt Rantapää-Dahlqvist2,
Lennart Jacobsson3
Institutionen för medicin, enhet för klinisk epidemiologi, Karolinska
Institutet, Stockholm 2 Institutionen för folkhälsa och klinisk medicin/reumatologi, Umeå Universitet, Umeå 3 Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning, Sahlgrenska Academin, Göteborgs Universitet, Göteborg
1
Background
The objective of the study was to evaluate the risk of acute coronary syndromes (ACS) in patients treated with tumour necrosis factor
inhibitors (TNFi) for rheumatoid arthritis (RA) compared with the
risk in bio-naïve RA patients and in the general population.
Methods
From the underlying national cohort of all individuals with two or
more outpatient diagnoses of RA we identified: 1) A cohort of patients with RA starting their first TNFi 2001-2010 as registered in
the Swedish Biologics Register (n=7,704, mean age 57.1 years, 75.9%
women) and 2) A matched bio-naïve RA comparator (3:1, n=23,112).
Furthermore, a matched comparator cohort (5:1, n=38,520) was
randomly selected from the Population Register. The outcome, incident ACS, was defined as a primary discharge diagnosis of myocardial infarction, or unstable angina, or myocardial infarction as
the underlying cause of death. Using three defined exposure windows, incidence rates were calculated and relative risks analysed
using Cox Proportional Hazards Regression models.
Results
Among patients ever exposed to TNFi 221 ACS were identified
(crude incidence rate 6.8 (5.9-7.7)/1,000 person-years). The fully
adjusted hazard ratios, HR (95%CI), for ever TNFi exposed compared with bio-naïve RA patients were 0.82 (0.70-0.95), comparing
bio-naïve RA with the general population 2.03 (1.80-2.29), and for
the TNFi cohort compared with the general population 1.61 (1.361.92) for the risk of ACS. Similar risk patterns were observed also
when the risk window was limited to time on treatment or the first
two years of treatment.
Conclusion
Treatment with TNFi was associated with a lower risk of ACS in
patients with RA. Compared with the general population the risk
of ACS in RA was increased, although less pronounced among the
TNFi exposed patients. This could be attributable to the TNFi per
se, or correspond to a higher degree of inflammatory control in the
treatment group.
Abstractnummer: 15
15
GOOD RESPONSE ON TUMOUR NECROSIS FACTOR INHIBITORS ARE ASSOCIATED WITH A DECREASED RISK OF ACUTE
CORONARY SYNDROMES IN PATIENTS WITH RHEUMATOID
ARTHRITIS
Lotta Ljung1,2, Lennart Jacobsson3, Solbritt Rantapää-Dahlqvist2, Johan Askling1
Institutionen för medicin, enheten för klinisk epidemiologi, Karolinska Institutet, Stockholm 2 Institutionen för folkhälsa och klinisk
medicin, Umeå Universitet, Umeå 3 Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning, Sahlgrenska
akademin, Göteborgs Universitet, Göteborg
1
Background
Inflammatory activity, as well as traditional cardiovascular risk
factors, has been suggested to underlie the increased risk of coronary disease in patients with rheumatoid arthritis (RA).
We therefore wanted to evaluate whether level of response to tumour necrosis factor inhibitors (TNFi) in RA are associated with
the risk of acute coronary syndrome (ACS).
Methods
All patients with RA and no previous ischemic heart disease who
started treatment with a first TNFi 2001-2010 as registered in
the Swedish Biologics Register were identified. Of the patients
(n=6,615) at risk for the exposure, i.e. EULAR response at 5+/-3
months, response data was available for 75% (n=4,938). For each
patient 5 matched referents were randomly selected from the Population Register.
Follow-up was maximized to 1 and 2 years, respectively. The outcome, incident ACS, was defined as a primary discharge diagnosis
of myocardial infarction or unstable angina, or myocardial infarction as the underlying cause of death. Incidence rates were calculated and adjusted Cox Proportional Hazard Regression models
were utilized for risk estimations.
Results
During the 1st year of follow-up 33 ACS occurred among the patients. The risk (HR 95%CI) of ACS for good responders compared
with none responders, fully adjusted, was 0.26 (0.08-0.83), and for
moderate responders compared with none responders 0.81 (0.36-
19
ABSTRACTS
1.79). Compared with the general population no increase in the risk
of ACS was observed among good responders, HR 0.74 (0.27-2.06).
The lower risk of ACS among good responders was noted also
during 2 years of follow-up.
Conclusion
Good EULAR response after 5 months of treatment with TNFi in RA
patients was associated with a significantly decreased risk of ACS.
In patients with good response on therapy no significant increase in
the risk of ACS was detectable in comparison with the risk in general
population during the 2 years after the evaluation.
Abstractnummer: 16
16
Rheumatoid Arthritis, a more severe disease than Psoriatic Arthritis? A comparison of diseAse activity in
patients with Psoriatic Arthritis and Rheumatoid Arthritis from the Swedish Early Psoriatic Arthritis registry (SwePsA) and the Swedish Rheumatology Quality Registry for early RA (SRQ).
Gerd-Marie Alenius1, Tomas Husmark2, Elke Theander3, Per
Larsson4, Mats Geijer5, Annika Teleman6, Ulla Lindqvist7
Umeå University, Department of Public Health and Clincal Medicin,
Rheumatology, Umeå 2 Falu Hospital, Department of Rheumatology,
Falun 3 Skåne University Hospital, Lund University, Department of
Rheumatology, Malmö 4 Karolinska University Hospital Huddinge,
Department of Rheumatology, Stockholm 5 Skåne University Hospital, Lund, Center for Medical Imaging and Physiology, Lund 6 Spenshult AB , Oskarström 7 Uppsala University, Department of Medical
Sciences, Rheumatology, Uppsala
1
Objectives
To compare the disease activity between psoriatic arthritis (PsA)
and rheumatoid arthritis (RA) in patients with early disease, and at
five year follow-up.
Methods
208 PsA patients included in SwePsA were compared with 381 RA
patients included in SRQ. The patients were matched (1:1-2) for
age, gender, year of inclusion in the registries and region of residence. Inflammatory parameters such a DAS28, its components,
CRP, HAQ, pain VAS and treatment, were measured at inclusion
and at 5 year follow-up. Single and multiple regression analyses
were performed and the stratified proportional hazards model has
been used to model the 1-2 or 1-1 matching designs depending on
the number of controls available for a case.
Results
At inclusion, patients with RA had higher DAS28, ESR, CRP, HAQ,
tender joint count (p<0.001, respectively), swollen joint count
(p=0.009), painVAS (p=0.003) and patient globalVAS (p=0.008)
compared to patients with PsA. After 5 years all parameters
had decreased. ESR was slightly higher in RA-patients (15.22 vs
12.36, p=0.046), while tender joint count now was higher in patients with PsA (3.58 vs 1.95, p< 0.000). DMARDs, steroids and
biologics were less common among PsA-patients than RA-patients at inclusion ( 40.9 % vs 84.7%, 9.1 vs 39.6 and 0.5 vs 2.8% respectively), and at 5-year-follow up (46.2% vs 80%, 8.2% vs 18.7%,
and 13% vs 37.7% respectively).
Conclusion
In this study, the disease activity at inclusion was higher in patients
with RA compared to PsA. At 5-year-follow up the disease activity
had decreased in both patient groups with significant differences
20
in only two of the parameters, ESR that was slightly higher in the
RA-patients and TJC that was higher in the PsA-patients. The patients in the RA-group were more often aggressively treated with
steroids, DMARDs and biologics indicating that RA may be a more
severe disease.
Abstractnummer: 17
17
VALIDITY OF ANKYLOSING SPONDYLITIS AND SPONDYLOARTHRITIS DIAGNOSES IN THE SWEDISH NATIONAL PATIENT
REGISTER.
U Lindström1, S Exarchou2, V Sigurdardottir3, B Sundström4, J
Askling5, JK Eriksson5, H Forsblad-d’Elia1, C Turesson2, LE Kristensen2, L Jacobsson1
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
2
Section of Rheumatology, Department of Clinical Sciences, Malmö,
Lund University, Malmö, Sweden 3 Department of Rheumatology,
Falun hospital, Falun, Sweden 4 Department of Public Health and
Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden
5
Clinical Epidemiology Unit, Rheumatology Unit, Department of
Medicine Solna, Karolinska Institutet, Stockholm, Sweden
1
Background
Epidemiological studies of spondyloarthritis (SpA) are scarce.
Using ICD-codes from the Swedish National Patient Register
(NPR) offers unique possibilities for such studies. For this purpose,
the validity of these ICD-codes needs to be determined.
Objectives
To validate the ICD-codes for ankylosing spondylitis (AS) and SpA
in the NPR against established classification criteria (modified
New York (mNY), ASAS, Amor and ESSG criteria).
Methods
All patients with an ICD-code of AS or SpA in the NPR 1966-2009
at a visit to a specialist in rheumatology or internal medicine, or
corresponding hospitalization, were identified (n=20074). Following a structured procedure to achieve geographical representativeness, 500 random patients with a registered diagnosis of AS
or SpA in 2007-2009 were selected. A structured review of clinical
records, with extraction of necessary information for the established classification criteria was performed and positive predictive
values (PPV) were calculated.
Results
In this cohort 11472 (34% women) patients had received an AS
diagnosis and 11004 (56% women) a SpA diagnosis. The overlap
group having received both types of diagnoses constituted 11% of
the population, and had similar frequencies for fulfillment of mNY
criteria, symptoms and signs of back disease as the group having
been coded as AS only. Of those being coded as AS only, the PPV for
fulfilling the mNY, any criteria set and any of the included criteria
elements were 70%, 89% and 96% respectively.
Of those with SpA (without AS ever) the corresponding PPV
values were 20%, 79% and 99% respectively.
Conclusion
A diagnosis of AS or SpA (without AS) had a high validity, suggesting that case identification based on ICD-codes in the Swedish
NPR can be used for epidemiological studies of these diseases.
ABSTRACTS
Abstractnummer: 18
18
Use of Biologics in Poly- and Dermatomyositis - A
National Register Study
John Svensson1, Anna Tjärnlund1, Maryam Dastmalchi1, Johan Askling1, Balsam Hanna2, Sara Magnusson Bucher3, Ingrid E Lundberg1
Karolinska Institutet
Universitetssjukhus
1
2
Sahlgrenska Universitetssjukhus
3
Örebro
Background/Purpose
Biologics have been used off-label in treatment of refractory polymyositis (PM) and dermatomyositis (DM). In this study we aimed to describe the use of biologics in patients with PM and DM
based on national registries in Sweden.
Methods
Patients were identified by linking the national patient care registers, the prescribed drug register, the Swedish Rheumatology
Quality register (SRQ) and the Swedish Myositis Network (SWEMYONET). Effectiveness was based on an overall assessment of
clinical outcome in the medical records, serum levels of creatine
phosphokinase (CPK) and prednisolone dose.
Results
63 patients treated with at least one biologic (36 PM, 27 DM, mean
age 60 (12) years, 45 women, 18 men) were identified at 11 different centers between 2001 and 2011. Rituximab (Mabthera®) was
the most often used biological agent: rituximab =42, abatacept
(Orencia®)=13, anakinra (Kineret®)=15, TNF-inhibitors (infliximab
(Remicade®), etanercept (Enbrel®)) =13 No new treatment with
anakinra (ANA) had been started after 2009 and no new treatment
with TNF-inhibitors (TNFi) had been started after 2003. In this
population we found an overall favorable response to rituximab
and abatacept in 2/3 of patients but less often to anakinra and
TNF-inhibitors (1/3 and 1/5 respectively). A statistically significant
decrease in CPK levels was found for RTX treated patients. All
other changes in CPK and prednisolone dose was non-significant.
Less than 15% of rituximab and abatacept treated patients stopped
treatment due to side effect while being more common for TNFinhibitors (30%) and anakinra (45%).
Conclusion
We found an increasing use of RTX and ABA in patients with PM
and DM. In this population, abatacept and rituximab was reported
as favorable more often than anakinra and TNF-inhibitors.
Abstractnummer: 19
19
Kontrollprovtagning vid metotrexatbehandling av
RA patienter
Johanna Karlsson Sundbaum1,2, Johan Back2, Niklas Lehto1,
Irene Vikman1, Eva Baecklund2
Inst för Hälsovetenskap Luleå Tekniska Universitet 2 Inst för medicinska vetenskaper Uppsala universitet
1
Bakgrund
Metotrexat (MTX) står för en stor del av den kontrollprovtagning
med dithörande uppföljning och åtgärder som görs inom reumatologin. För att eventuellt kunna förbättra dessa rutiner ville vi undersöka förekomsten av stegrade ALAT-värden, patientkaraktäristika
hos dem med och utan avvikelser, följsamhet till provtagningsruti-
ner och vilka åtgärder labavvikelser leder till hos MTX-behandlade
RA patienter på vår enhet.
Metod
RA patienter med MTX insatt jan 2005-april 2013 på reumatologen, Akademiska sjukhuset, Uppsala ingick i studien. Information
om klinik och provtagning inhämtades från journal kompletterat
med telefonenkät om alkoholintag och BMI. För jämförelser mellan grupperna användes oberoende T-test och chi2-test.
Resultat
Totalt 214 patienter ingick i studien. Medelbehandlingstiden med
MTX var 225 veckor (8-456). ALAT-stegring (> övre referensvärde) sågs hos 85 (36 %) patienter efter i medel 82 veckor (1-379) vid
en medeldos MTX på 15 mg (7,5–25). ALAT > 2x övre referensvärdet uppmättes hos 33 (39 %). Totalt avbröt 8 (9 %) behandlingen
pga. ALAT-stegring. ALAT-stegring var signifikant kopplad till
kvinnligt kön, högre BMI och tidigare känd ALAT-stegring.
Följsamheten till provtagning var sämst under år 1,64 % av patienterna följde rutin, men bra under år 2 och 3 (90 % följde rutin).
Efter förhöjt värde genomfördes ett antal åtgärder (uppehåll, sänkt
dos, höjd Folacindos, utsättande av annat läkemedel, utredning) eller ingen åtgärd alls, utan struktur eller konsekvent koppling till
uppmätt ALAT-värde.
Konklusion
Med dagens behandlingsregim är ALAT-stegring vanlig (36 %)
men leder sällan till utsättning av MTX (9 %). Stor spridning i tid
för ALAT-stegring motiverar långtidsuppföljning. Behov finns för
strukturering av åtgärder efter avvikande labsvar. Ytterligare analys av detta material kan ge underlag för detta.
Abstractnummer: 20
20
HIGH SERUM CHOLESTEROL PREDICTS RHEUMATOID ARTHRITIS IN WOMEN
Carl Turesson1,2, Ulf Bergström1,2, Mitra Pikwer2,3, Jan-Åke
Nilsson1,2, Lennart Jacobsson2,4
Reumatologiska kliniken, Skånes Universitetssjukhus 2 Sektionen
för Reumatologi, Institutionen för Kliniska Vetenskaper, Malmö,
Lunds Universitet 3 Reumatologkliniken, Mälarsjukhuset, Eskilstuna
4
Avdelningen för Reumatologi och Inflammationsforskning, Sahlgrenska Akademin, Göteborgs Universitet
1
Background
Lipid metabolism and hormonal factors may contribute to the development of rheumatoid arthritis (RA). The purpose of this study
was to examine sex-specific effects of serum cholesterol on the future risk of RA.
Methods
Between 1974 and 1992, 33346 subjects (22444 men and 10902
women) were included in the Malmö Preventive Medicine Program (MPMP). Serum cholesterol was assessed using fasting
blood samples. Individuals who developed RA after inclusion in
the MPMP were identified by linkage to several RA registers and
a structured review of the medical records. Four controls for each
validated case, matched for sex, year of birth and year of screening,
who were alive and free of RA when the index person was diagnosed with RA, were selected from the MPMP register. The impact of
serum cholesterol on the risk of RA was examined in conditional
logistic regression models, stratified by sex.
21
ABSTRACTS
Results
There were 290 incident cases of RA [151 men and 139 women;
median time from inclusion to RA diagnosis 12 years (range 1-28);
mean age at diagnosis 60 years . Cholesterol levels did not differ
between men who subsequently developed RA and controls (mean
5.66 vs.5.64 mmol/l). By contrast, women with a diagnosis of RA
during the follow-up had higher cholesterol levels at baseline compared to controls mean 6.04 vs. 5.71 mmol/l; OR 1.54 per standard
deviation (95 % CI 1.22-1.94)]. The association between higher cholesterol and subsequent development of RA in women remained
significant in multivariate analyses adjusted for smoking (p=0.001)
or early menopause (at age <46 years) (p=0.01).
Conclusions
A higher serum cholesterol was associated with increased risk of
RA in women, but not in men. This suggests that sexspecific exposures modify the impact of lipids on the risk of RA, and implicates
early metabolic pathways in the etiology of RA.
Abstractnummer: 21
21
Interaktion mellan saltintag och rökning ökar risken för reumatoid artrit
Björn Sundström1, Ingegerd Johansson2, Solbritt RantapääDahlqvist1
Umeå Universitet, Inst. f. Folkhälsa och klinisk medicin/reumatologi 2 Umeå Universitet, Inst.f.Kariologi
1
Bakgrund
Studier på mänskliga celler och djurmodeller har påvisat att natriumklorid kan initiera patogena Th17 celler genom ett saltkänsligt
kinas (SGK1). Därför är det av intresse att studera huruvida natriumintag påverkar risken för att insjukna i reumatoid artrit (RA).
Material och metod
En nestlad fall-kontrollstudie genomfördes på basis av prospektiva
data insamlade inom Västerbottensprojektet (VIP) mellan år 1991
och 2011. I studien ingick 386 fall som tidigare hade uppgivit sina
kostvanor inom VIP före debut av första symtom på RA. Dessa jämfördes med 1886 matchade kontroller ifrån samma databas.
Resultat
Vid analys av alla fallen som homogen grupp sågs inga signifikanta
samband mellan saltintag och risk för att utveckla RA. I analyser
stratifierade för rökvanor (rökare och icke-rökare) vid tidpunkten för undersökningen så mer än fördubblade saltintaget risken
att insjukna i RA bland rökare (OR = 2,26, 95% CI 1,06-4,81). Detta
sågs inte hos icke-rökare. Vid interaktionsanalys av rökning och
den tredjedel av fallen som hade högst saltintag sågs att 54% av den
ökade risken för att utveckla RA kunde hänföras till en interaktion
mellan rökning och saltintag (Attributable proportion of risk due
to interaction, AP: 0,54 95% CI 0,26-0,82). Motsvarande överskjutande relativ risk av interaktion (RERI) var också signifikant (1.34,
95% CI 0.37-2.32). Dessa andelar av riskerna ökade ytterligare vid
avgränsning av analyserna till de fall som var positiva för anti-CCP
och/eller HLA-SE.
Slutsats
Ett högre saltintag bland rökare var associerat med en ökad risk för
att utveckla RA. Denna interaktion mellan saltintag och rökning
kan ge nya insikter i patogenesen för RA. Eftersom saltintaget i hög
grad är korrelerat till konsumption av livsmedel som till exempel
kött, frukt och grönsaker så kan dessa resultat även ha betydelse för
22
analyser av kostens betydelse för att utveckla RA.
Abstractnummer: 22
22
Reduced sick leave in today’s early RA patients
compared to 10 years ago, The Swedish TIRA project
Mathilda Björk1, Thomas Skogh2, Magnus Husberg3, Ingrid
Thyberg4
Rehabenheten, HMC, Universitetssjukhuset i Linköping, Landstinget i Östergötland 2 Avdelningen för reumatologi/AIR, IKE, Hälsouniversitetet i Linköping 3 CMT, Hälsouniversitetet i Linköping
4
Reumatologkliniken, HMC, Universitetssjukhuset i Linköping,
Landstinget i Östergötland
1
Background
Ten years ago rheumatoid arthritis (RA) was associated to extensive sick leave during the years after diagnosis despite early instituted disease modifying anti rheumatic drugs (DMARD:s). Since
then the treatment strategies have undergone big changes and biological agents have been introduced.
Objectives
To compare sick leave in early RA today compared to10 years ago.
Methods
320 patients were included in the Swedish early RA cohort (TIRA1)
during 1996-1998 and 522 patients were included 2005-2008 in the
TIRA2 cohort. The prescription of traditional DMARD:s was more
frequent in TIRA2 already at inclusion but there were no differences in DAS28 between two cohorts that timepoint. The 120 patients (76% women) that were still participating in TIRA1 at 3-year
follow-up and that were ≤ 64 years were included in the present
study together with the corresponding 275 patients (74% women)
in TIRA2. Sick leave data (sickness benefit and disability pension)
were obtained for patients three years before until three years after
inclusion (diagnosis).
Results
The proportion of patients on sick leave started to increase during
the year before diagnosis to 40% in TIRA1 and 44% in TIRA2.
During the year after diagnosis this number increased to 56% in
TIRA1 and 50% in TIRA2. In TIRA2 the number decreased during
the second (36%) and third year (30%), in contrast to TIRA1 where
sick leave remained rather stable (54-52%).
Conclusions
The far lower sick leave rate seen today after a diagnosis of RA,
compared to the situation 10 years ago, cannot be explained by differences in sick leave during the year before diagnosis. Although
sick leave is lower today, the sick leave rate in TIRA2 is still high
compared to the general population. This highlights a need to develop efficient multiprofessional intervention strategies in addition to
modern anti-rheumatic pharmacotherapy regimens.
Abstractnummer: 23
23
COMORBIDITY IN EARLY RHEUMATOID ARTHRITIS. DOES INFLAMMATION MATTER?
Solveig Wållberg Jonsson, Lena Innala, Clara Sjöberg, Anna
Södergren, Bozena Möller, Torgny Smedby, Staffan Magnusson, Solbritt Rantapää Dahqvist
1
Inst. för Folkhälsa och klinisk medicin/Reumatologi, Umeå Universitet,
ABSTRACTS
Umeå 2 Reumatologkliniken, Sunderby sjukhus, Luleå 3 Reumatologkliniken, Östersunds sjukhus 4 REumtologkliniken, Sundsvalls sjukhus
Background
Patients with rheumatoid arthritis (RA) suffer from comorbidities
that contribute to a shortened lifespan. Inflammation is of importance for the development of cardiovascular disease, but little is
known on its relationship with other comorbidities in RA.
We examined the prevalence of comorbidities in early RA and the
role of inflammation in this context.
All patients with early RA (symptom duration <12 months) in
Northern Sweden are since 1995 included in a prospective study on
co-morbidities. By now 950 patients have been included.
At the time of this compilation, 715 patients were followed-up of
whom 498 had been ill for ≥ 5 years. Data on comorbidities, disease
activity, x-ray (hands/feet), laboratory samples (autoantibodies, inflammatory variables) and pharmacological therapy were collected
in record studies and further validated using a questionnaire at RA
onset (T0) and after 5 years of disease (T5).
Results
53% had one or more comorbidities at RA onset. After 5 years, 41%
developed at least one new comorbidity. At T0, the most common
comorbidities were: hypertension (26.7%), obstructive pulmonary
disease (13.4%), diabetes (7.1%), hypothyroidism (7.0%) and malignancy (5.2%). At T5, the most common new comorbidities were: hypertension (14.3%), malignancy (7.6%), stroke/TIA (5.0%), myocardial infarction (4.8%) and osteoporosis (4.4%). Univariate regression
analyses showed that age (p< 0.001), ESR (p<0.01), extra-articular
disease (p<0.01), corticosteroids (p<0.001) were associated with a
new comorbidity during 5 years. Female gender and biologics reduced this risk (p<0.01 for both). In a multiple regression model adjusted for sex, age, corticosteroid treatment and smoking, ESR was
associated with new endocrine disease during 5 years.
Conclusion
There was substantial comorbidity among RA patients already at
disease onset and considerable new comorbidity during the first
five years of disease. Measures of disease activity were associted
with occurrence of comorbidity.
Abstractnummer: 24
24
ASSOCIATIONS OF ANTIBODIES AGAINST CITRULLINATED PEPTIDES WITH HLA SHARED EPITOPE, PTPN22 1858T VARIANT,
AND SMOKING IN INDIVIDUALS PRIOR TO THE DEVELOPMENT OF RHEUMATOID ARTHRITIS
Heidi Kokkonen1, Mikael Brink1, Monika Hansson2, Linda
Mathsson3, Ewa Lassen4, Johan Rönnelid3, Lars Klareskog2,
Solbritt Rantapää Dahlqvist1
Institution of Public Health and Clinical Medicine/Rheumatology,
Umeå University, Umeå 2 Rheumatology Unit, Karolinska University
Hospital, Stockholm 3 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 4 Transfusional Medicin, University Hospital, Umeå.
1
Abstractnummer: 25
25
IgG anti-CCP SUBCLASS DISTRIBUTION AND ISOTYPE USAGE
IN EARLY RHEUMATOID ARTHRITIS
1
Hälsouniversitetet Linköping, AIR / Reumatologi
Introduction
In this study we investigate patterns of IgG-subclass utilization regarding antibodies against cyclic citrullinated peptides (anti-CCP)
among patients with rheumatoid arthritis (RA). The patients were
sub-grouped based on smoking-habits, ‘shared epitope’ (SE) genotype and immunoglobulin (Ig)A anti-CCP status.
Materials & Methods
Serum samples were obtained from 498 patients with recent-onset
RA (<12 months) at the time of inclusion in the Swedish TIRA-2
cohort (‘Early Intervention in Rheumatoid Arthritis’). IgG antiCCP subclasses were measured by enzyme-linked immunosorbent
assay. Presence of the different IgG anti-CCP subclasses was then
compared with smoking habits, SE genotype and IgA anti-CCP status.
Results
The proportions of patients testing positive for the respective IgG
anti-CCP subclass (1-4) were: 72, 31, 43, 55%. The corresponding
results among ever-smokers were: 74, 39, 49, 56%; never-smokers:
64, 25, 39, 46%; SE+: 82, 33, 49, 62%; SE−: 45, 18, 30, 34%; IgA antiCCP+: 100, 70, 86, 95%; IgA anti-CCP−: 62, 17, 27, 41%. No significant differences were seen between ever and never-smokers. The
proportion of patients positive for IgG1, IgG3 and IgG4 anti-CCP
were significantly higher among SE+ compared to SE−. The IgA
anti-CCP+ subgroup showed significantly higher proportions of
IgG1-4 anti-CCP as well as higher IgG subclass usage compared to
the IgA anti-CCP− subgroup.
Conclusion
Our results indicate that smoking per se does not exert a significant
impact on the IgG anti-CCP subclass repertoire. IgG2 anti-CCP
was unaffected by SE whereas the other subclasses were, especially IgG1 and IgG4. IgA anti-CCP strongly associated with a wide
IgG anti-CCP repertoire, reflected by the high isotype utilization.
However, due to the relatively small study groups, additional studies on larger patient materials should be performed before definite conclusion can be made.
Abstractnummer: 26
26
PREDICTIVE POTENTIAL OF SURVIVIN MEASURED IN UNSELECTED SERUM SAMPLES REFFERED TO THE CLINICAL
IMMUNOLOGY LABORATORY FOR DETECTION OF RF AND/
OR ANTI-CCP ANTIBODIES – ONE YEAR EXPERIENCE FROM
THE VÄSTRA GÖTALAND REGION
Minna Turkkila1, Malin Erlandsson1, Rille Pullerits1, Maria Bokarewa1
Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Gothenburg
1
Abstractnummer: 27
27
Serum survivin in early rheumatoid arthritis – results from the SWEFOT trial
Adrian Levitsky1, Malin Erlandsson2, Ronald van Vollenhoven1,
Maria Bokarewa2
1
ClinTRID, Karolinska Institutet 2 Sahlgrenska University Hospital
Anders Johansson1, Thomas Skogh1, Klara Martinsson1
23
ABSTRACTS
Abstractnummer: 28
28
INTRACELLULAR SURVIVIN IS DECREASED IN CD4+ T-CELLS OF
RHEUMATOID ARHTRITIS PATIENTS WITH HIGH SERUM SURVIVIN
Nicola Filluelo Cavallini1, Minna Turkkila1, Mikael Brisslert1,
Karin Andersson1, Maria Bokarewa1
Department of Rheumatology and Inflammation Research, University of Gothenburg
1
Background
Survivin has recently emerged as a specific and sensitive biomarker in RA. We have recently shown that serum survivin (sS) is associated with severity of the disease and with joint destruction.
Objective
We studied intracellular expression of survivin on the peripheral
T-cell populations and its relation to serum levels of survivin.
Methods
Serum and intracellular expression of survivin was analysed in 144
RA patients (age 21-71 years, disease duration 1-49 years) using ELISA and qPCR respectively. Patients were grouped according to sS
levels (cut-off >0.45 ng/mL). In 18 RA patients the intracellular protein expression of survivin was studied on CD4+ and CD8+ T-cells
using flow cytometry. Gating strategy defined Survivin+ or survivinhi populations, and also effector and memory T-cell populations.
Results
Intracellular mRNA levels of survivin were similar in sS- (n=68)
and sS+ (n=76) patients. Intracellular survivin was present in 88
% CD4+ T-cells and in 85 % CD8+ T-cells. The survivinhi subset
comprised 0.5-11 % of the T-cells and was enriched in the CD4+
effector (CD62Lneg) population compared to central memory and
naïve CD4+ T-cells. Survivinhi cells are mostly found in CD4+
Tcells, which also have a significantly larger population than CD8+
T-cells. The survivin+ subset within the effector CD4+ T-cells was
characterised by a selective expression of Bcl6, a transcriptional
regulator of follicular T-cells. The survivin+CD4+ subset were
smaller in sS+ patients compared to sS- patients, and were inversely correlated to sS levels of the patients. The sS+ patients had lower
Bcl6 mRNA levels compared to sS- patients.
Conclusions
CD4+ effector T-cells are distinguished by the enhanced expression of
survivin in RA patients. Patients with high serum levels of survivin had
a smaller fraction of Surv+Bcl6+ effector T-cells, which may potentially indicate a cytolytic origin of the extracellular survivin.
Abstractnummer: 29
29
SURVIVIN BUT NOT FMS-LIKE TYROSINE KINASE LIGAND
(FLT3L) IS UP-REGULATED BEFORE ONSET OF RHEUMATOID
ARTHRITIS
Maria Bokarewa2, Mikael Brink1, Malin Erlandsson2, Solbritt
Rantapää Dahlqvist1
Institutionen för Folkhälsa och Klinisk Medicin, Umeå Universitet 2
Avdelningen för reumatologi och inflammationsforskning, Göteborgs
Universitet
1
Background
Antibodies against citrullinated peptides (anti-CCP) and incre24
ased levels of cytokines precede the development of rheumatoid
arthritis (RA) by several years. Recently, the proteins survivin and
Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as
biomarkers of RA associated with joint destruction. The aim was to
investigate the potential of survivin and Flt3L as predictors of RA
in samples from patients prior to onset of symptoms.
Methods
This study included 47 individuals sampled before onset of RA
(median 2.5 years (IQR 4.5) and 155 matched controls, all were donors to the Medical Biobank of Northern Sweden, and 36 RA patients. Levels of anti-CCP, survivin and Flt3L were measured using
ELISAs and 29 cytokines/chemokines by multiplex detection.
Results
Levels of survivin were increased in presymptomatic individuals compared with controls (p=0.003), whilst the levels of
Flt- 3L were similar. The frequency of survivin positivity in the
pre-symptomatic individuals was increased compared with the
controls (36.2 vs.14.2%, p=0.001) and predicted disease development (OR=3.4[95%CI 1.6-7.2]). The frequency of survivin and Flt3L
in RA patients was increased compared with the controls (both,
p<0.0001, OR=12.1[95%CI, 5.3-27.6] and OR=11.0 [3.9-30.9], respectively). Anti-CCP positive pre-symptomatic individuals and
patients had significantly higher levels of survivin compared with
anti-CCP2 negative individuals. In pre-symptomatic individuals,
survivin correlated with IL-12, IL-1Beta and IL-9 whereas Flt3L
correlated to a significantly broader spectrum of cytokines in RA
patients.
Conclusion
Proto-oncogene survivin was increased in individuals prior to onset of symptoms of RA and was correlated to cytokines suggesting
its role at pre-clinical stages of the disease.
Abstractnummer: 30
30
IN EARLY RHEUMATOID ARTHRITIS, THE 12 INDIVIDUAL
BIOMARKERS THAT COMPRISE THE MULTIPLEBIOMARKER
DISEASE ACTIVITY SCORE RELATE DIFFERENTIALLY TO CLINICAL RESPONSE AND RADIOGRAPHIC PROGRESSION: RESULTS
FROM A RANDOMIZED TRIAL
Karen Hambardzumyan1, Saedis Saevarsdottir 1, Rebecca Bolce2, Kristina Forslind3, Sofia Ernestam4, Ingemar Petersson5,
Pierre Geborek5, Ronald van Vollenhoven1
Karolinska Institutet 2 Crescendo Bioscience Inc. 3 Section of Rheumatology, Department of Medicine, Helsingborg General Hospital 4
Karolinska University Hospital 5 Lund University
1
Background
In early rheumatoid arthritis (eRA), clinical and radiographic predictors would be very useful for optimizing available therapies. For
these purposes, individual biomarkers and their combination in
the multi-biomarker disease activity (MBDA, Vectra DA) test, was
evaluated using serum from the eRA patients from the SWEFOT
trial. The objective of this study was to assess the 12 individual biomarkers that comprise the MBDA score at baseline (BL) as predictors of clinical response at 3 months and radiographic progression at 1 year in eRA.
Methods
Analyses were performed for patients from the SWEFOT trial who
had BL and 3-month data of DAS28-ESR), the MBDA score and the
12 individual biomarkers at BL; and for a subset of patients who
ABSTRACTS
also had radiographs at BL and 1 year (assessed using the Van der
Heijde modified Sharp score [SHS]). Patients with DAS28 > 3.2 at
3 months were considered clinical non-responders, and patients
with a change in SHS > 0 as radiographic progressors.
Group comparisons of biomarkers were performed by Mann-Whitney U test.
Results
Clinical non-responders had significantly higher BL values for CRP
and IL-6 compared to responders. TNF-R1 and VCAM-1 were significantly lower for non-responders, while other biomarkers and
the MBDA did not differ. The patients who progressed radiographically had, at BL, significantly higher MBDA scores, inflammatory
biomarkers (CRP, SSA and IL-6), MMP-1, MMP-3 and TNF-R1, as
well as a trend towards higher VEGF.
Conclusion
In eRA patients treated with MTX, some individual biomarkers at
BL may help in predicting clinical non-responsds after 3 months of
MTX therapy. Other biomarkers, as well as the MBDA score, may
identify patients at higher risk for radiographic progression during
the first year of therapy. Thus biomarkers can differentially predict
aspects of disease course in eRA.
Abstractnummer: 31
31
A MULTI-BIOMARKER DISEASE ACTIVITY SCORE CORRELATES
WITH RADIOGRAPHIC PROGRESSION IN EARLY RHEUMATOID
ARTHRITIS: RESULTS FROM A RANDOMIZED TRIAL
Karen Hambardzumyan1, Rebecca Bolce2, Kristina Forslind3,
Saedis Saevarsdottir1, Ingemar Petersson4, Pierre Geborek4,
Sofia Ernestam5, Ronald van Vollenhoven1
Karolinska Institutet 2 Crescendo Bioscience Inc. 3 Section of Rheumatology, Department of Medicine, Helsingborg General Hospital 4
Lund University 5 Karolinska University Hospital
1
Background
In early rheumatoid arthritis (eRA), predictors of radiographic
damage are needed for optimal targeting of therapy. It has been
suggested that combining various biomarkers may improve this
prediction.
Objective
To assess the baseline MBDA score as a predictor of radiographic
progression over one year in eRA patients from the SWEFOT trial.
Methods
Analyses were performed for 235 patients from SWEFOT with baseline, month 3 (n=220) and week 52 (n=235) assessments of DAS28,
DAS28-CRP, CRP, MBDA score, and radiographs at baseline and 1
year (using the Van der Heijde modified Sharp score [SHS]). Associations between disease activity indices and radiographic progression at one year were evaluated using Wald’s chisquare test.
Spearman’s correlation coefficients (r) were determined for the BL
disease index scores versus radiographic progression (deltaSHS
>5) over 1 year.
Results
Baseline MBDA score correlated with deltaSHS from baseline to 1
year: r = 0.271 (p<0.001); correlations of DAS28, DAS28-CRP, and
CRP with deltaSHS were weaker: r = 0.063, 0.014, and 0.178, respectively (p=NS, p=NS, p=0.006). In bivariate analyses adjusting
for DAS28 or CRP, MBDA had a significant additive value to prediction of radiographic progression at one year (p<0.01). Of the 43
patients with deltaSHS > 5, 98% had a high baseline MBDA score,
77% a high DAS28 (>5.1) and 49% a high CRP (>3mg/dL). Of patients
with a high MBDA score at baseline, 21% had SHS progression, versus 3% and 0% for moderate and low MBDA, respectively (p<0.04).
Conclusion
The association of a high MBDA score at baseline with higher risk
of radiographic progression in eRA patients, and low and moderate MBDA score with lower risk was stronger than that of CRP or
DAS28. Thus, in untreated eRA, MBDA may help identify patients
at low versus high risk of radiographic progression and thereby
support rational treatment choices.
Abstractnummer: 32
32
SIGNIFICANT DIFFERENCES IN DISPENSED DOSES WERE OBSERVED BETWEEN SELF-ADMINISTERED TNFINHIBITORS
Esbjörn Larsson1,2, Mats Ekelund2, Anders Berglund2
1
Reumatologkliniken, Karolinska Sjukhuset 2 Pfizer AB Sverige
Background
Neutralizing anti-bodies have been observed with self-administered TNF-inhibitors, adalimumab, golimumab and cerolizumab
pegol but not with etanercept. Neutralizing anti-bodies may cause
loss of efficacy and subsequent increases of dose. Dose increases
may be initiated by the doctor or occur as the patient shortens the
interval between self-injections. We aimed to study a combined
measure of dose increase that captures both prescribed increases
in dose and patient initiated increases in dose.
Materials and methods
This retrospective study retrieved information from the Swedish
Prescribed Drugs Register among adult patients for the first time
prescribed with etanercept, adalimumab, golimumab or certolizumab pegol by a rheumatologist between May 2010 and Mars 2013.
The ratio between the observed and the expected dispensed dose
based on the recommended dose according to the SMPC by TNF
blockers were evaluated during follow up.
Results
Data from 2,137 patients on etanercept, 2,181 on adalimumab, 1,102
on golimumab and 1,161 certolizumabpegol were analyzed.
During follow up the ratio between the observed versus the expected dose in relation to time was 0.96 (CI 95% 0.95-0.97) for etanercept, 0.99 (CI 95% 0.94-1.03) for certolizumab pegol, 1.013 (CI 95%
1.00-1.03) for adalimumab, and 1.05 (CI 95% 1.04-1.07), respectively. The ratio between the TNF blockers were significant between
etanercept and adalimumab (p<0.001), golimumab (p<0.001) but
not for certolizumab pegol (p=0.189)
Conclusions
New and continuing patients on etanercept had a significantly
lower observed versus expected dose ratio in comparison with patients on golimumab and adalimumab. Cost comparisons based on
actual doses may be more relevant to payers than cost comparisons
based on labelled doses.
Abstractnummer: 33
33
Reduced relative risk of serious pneumococcal infections after immunisation with heptavalent pneumococcal conjugate
vaccine in arthritis patients on different treatments including
methotrexate and TNF-inhibitors.
25
ABSTRACTS
Johanna Nagel1, Pierre Geborek1, Tore Saxne1, Göran Jönsson2, Martin Englund3,4, Ingemar Petersson3, Jan-Åke Nilsson1, Meliha Crnkic Kapetanovic1
Department of Clinical Sciences, Lund, Section of Rheumatology,
Skåne University Hospital, Kioskgatan 3, Lund, SE-221 85 Sweden 2
Dept of Clinical Sciences Lund, Section of Infectious Diseases, Lund
University, Sweden 3 EpiCentrum Skåne, Skane University Hospital,
Department of Orthopedics, Clinical Sciences Lund, Lund University, Sweden 4 Clinical Epidemiology Research & Training Unit, Boston
University School of Medicine, Boston, MA, USA
1
Abstractnummer: 34
34
EARLY DEXAMETHASONE TREATMENT IMPROVES SURVIVAL
IN ENDOTOXEMIC SHOCK
Maria Bergquist1,2, Merja Nurkkula1, Christian Rylander3, Göran Hedenstierna2, Catharina Lindholm1
Avd för Reumatologi och Inflammationsforskning, Göteborgs Universitet 2 The Hedenstierna Laboratory, Uppsala Universitet 3 Department of Anaesthesia & Intensive Care, Sahlgrenska Universitetssjukhuset
1
Introduction
Severe sepsis is associated with high mortality despite antibiotic
treatment. The role of glucocorticoid treatment in severe sepsis
and septic shock remains controversial. The reasons for the contradictory outcomes of glucocorticoid treatment in clinical trials
are unknown. A possible mechanism behind glucocorticoid resistance could be decreased expression and/or function of glucocorticoid receptors (GR).
Objectives
To study the expression and function of GR in endotoxemic shock
and to investigate the relation between GR expression and function
with the response to glucocorticoid therapy.
Methods
Male C57BL/6J mice were given LPS intraperitoneally. Blood and
spleen cells were collected for analyses of GR expression in T cells
(CD4+ and CD8+), B cells, monocytes, and neutrophils by flow cytometry. GR function was assessed by in vitro binding of FITC-labelled dexamethasone and nuclear translocation by ImageStream.
The effect of dexamethasone treatment on mortality was studied.
Results
Blood and spleen B cells and neutrophils had increased GR expression in contrast to the decreased expression in CD4+ T lymphocytes and monocytes (p<0.05). The dexamethasone binding capacity
was increased in B cells in blood and spleen (p≤0.02).
Interestingly, spleen neutrophils bound less dexamethasone
(p=0.01) in spite of higher GR expression. On day 1 after LPS administration, the translocation ability was increased compared to
healthy controls but reduced on day 2 compared to day 1 in all cells
(p<0.0001). Dexamethasone administered 2 hours after LPS administration resulted in reduced mortality compared to when dexamethasone treatment was started at 12 hours (p=0.02) and when no
dexamethasone treatment was given (p=0.02).
Conclusion
Steroid treatment in endotoxemic shock is only effective when given early. Neutrophils have reduced ability to bind dexamethasone
during endotoxemic shock despite their increased GR expression.
This, in combination with the increased numbers of neutrophils
26
seen in sepsis, may explain why steroid treatment is only beneficial
when administered early.
Abstractnummer: 35
35
BAZEDOXIFENE AND ESTROGEN IN COMBINATION EFFICIENTLY INHIBITS EXPERIMENTAL ARTHRITIS WITH MINIMAL UTERINE STIMULATION
Annica Andersson1, Angelina Bernardi1, Alexandra Stubelius1, Merja Nurkkala-Karlsson1, Louise Grahnemo1, Hans Carlsten1, Ulrika Islander1
Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden
1
Background
Estrogen treatment, as in hormone-replacement therapy, has been
reported to be beneficial in postmenopausal RA, however, is associated with certain side effects. Bazedoxifene (BZA), a selective
estrogen-receptor modulator, combined with estrogens, is used as
a tissue selective estrogen complex (TSEC) to treat menopausal
symptoms and prevent bone loss without stimulating the breast or
endometrium. The aim of this study was to investigate effects of
TSEC in experimental arthritis.
Methods
Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis (CIA) and therapeutically treated with s.c. injections of 17beta-estradiol only (E2; 0.1 and 0.5 microg/day), BZA
only (24 microg/day), BZA + E2 (24 + 0.1 microg/day), BZA + E2
(24 + 0.5 microg/day) or vehicle. Arthritis development was macroscopically assessed days 17-42 after first immunization anduteri
were weighed at termination.
Results
Mice treated with BZA + E2, or E2 only, displayed dramatically
reduced arthritis severity (AUC day 17-42; p< 0.001) and decreased incidence of arthritis (p< 0.01 day 28-31, p< 0.001 day 33-42),
compared to vehicle controls. Importantly, mice treated with BZA
+ E2 showed minimal uterine growth, with significant reductions
in mean uterine weights by 79% for BZA + E2 0.1 microg compared
to E2 only, and 69% for BZA + E2 0.5 microg vs. E2 only.
Conclusions
TSEC (bazedoxifene and estrogen) is efficiently inhibiting experimental autoimmune arthritis and diminishes estradiolmediated uterine side effects. The findings in this study are of importance regarding
the treatment regimen of women with RA experiencing concurrent
menopausal symptoms and increased risk for osteoporosis.
Abstractnummer: 36
36
CHEMOKINE-MEDIATED REGULTION OF TH17-CELL MIGRATION
AS A NOVEL MECHANISM FOR ESTROGEN-INDUCED AMELIORATION OF EXPERIMENTAL ARTHRITIS
Annica Andersson1, Alexandra Stubelius1, Merja Nurkkala-Karlsson1, Cecilia Engdahl1,2, Malin Erlandsson1, Louise Grahnemo1, Marie K Lagerquist2, Hans Carlsten1, Ulrika Islander1
Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden 2 Centre for Bone and Arthritis Research,
Department of Internal Medicine and Clinical Nutrition, The Sahl-
1
ABSTRACTS
grenska Academy, University of Gothenburg, Sweden
Background
The incidence and progression of many autoimmune diseases
are gender-biased, which partly might be explained by the immune-modulating properties of endocrine hormones. Estrogen
treatment, as in hormone-replacement therapy, has been shown
to be beneficial in rheumatoid arthritis (RA), although the mechanisms involved are mostly unknown. Pro-inflammatory T helper 17
(Th17) cells have emerged as key players in driving RA, although
it has not been studied if estrogen modulates Th17 cells in this disease. Therefore, the aim of this study was to investigate effects of
estrogen on Th17 cells in experimental arthritis.
Methods
Female ovariectomized DBA/1 mice, treated with 17beta-estradiol
(E2; 0.83mikrog/day) or placebo, were subjected to collagen-induced arthritis (CIA) and Th17 cells in joints and lymph nodes were studied at several time points, with flow cytometry and IL-17 ELISPOT.
Results
E2-treated mice with established CIA showed reduced severity and
incidence of arthritis and fewer Th17 cells in joints compared to placebo controls. Interestingly, mice treated with E2 displayed accumulation of Th17 cells in lymph nodes during the induction phase of CIA,
which was associated with an up-regulation of chemokine receptor
6 (CCR6) on lymph node Th17 cells as well as increased expression of the corresponding chemokine CCL20 within lymph nodes.
Conclusions
The E2-induced retention of Th17 cells within the lymph nodes in
CIA, caused by interference with the CCR6-CCL20 pathway, suggests a novel mechanism in estrogen-mediated inhibition of arthritis. Our study presents new important perspectives on the effects
of estrogen on the immune system, and the CCR6-CCL20-induced
retention of Th17 cells in lymph nodes per se could be implicated
in development of new treatment strategies in RA.
Abstractnummer: 37
37
with las, bza, ral, 17β-estradiol (E2) or vehicle. Bone marrow and
spleen cells were phenotyped by flow cytometry and antibody-producing cells were quantified using ELISPOT assay.
Results
As expected, treatment with E2 caused a decrease of B cells at all
developmental stages from pro-B cells (in bone marrow) to transitional 1 B cells (in spleen). However, treatment with las and bza
only led to a significant decrease in two distinct B cell populations; immature B cells in bone marrow and transitional 1 B cells in
spleen. Also, in contrast to E2, treatment with las and bza did not
result in increased numbers of antibody-producing cells.
Conclusion
LasandbzadifferfromE2byretainingnormalnumberofcellsatmostBcell
stages during B lymphopoesis. Also, las and bza do not cause the increase
in antibody production observed after treatment with E2.
Abstractnummer: 38
38
B-REGULATORY CELLS ARE FUNCTIONALLY IMPAIRED IN
PATIENTS WITH RHEUMATOID ARTHRITIS AND IN THEIR
FIRST DEGREE RELATIVES COMPARED WITH CONTROLS
Mikael Brink1, Lisbeth Ärlestig1, Solbritt Rantapää Dahlqvist1,
Kristina Lejon2
Institutionen för Folkhälsa och Klinisk Medicin, Umeå Universitet 2
Institutionen för Klinisk Mikrobiologi, Umeå Universitet
1
Abstractnummer: 39
39
Does evaluation of hand bone loss by Digital x-ray
radiogrammetry within the first 3 months after diagnosis of rheumatoid arthritis identify patients at
risk for radiological progression?
Ewa Berglin1, Katrine Åhlström Riklund2, Solbritt Rantapää
Dahlqvist1
ROLE OF LASOFOXIFENE AND BAZEDOXIFENE IN B CELL DEVELOPMENT AND FUNCTION
1
Inst. för folkhälsa och klinisk medicin/Reumatologi 2 Inst. för strålningsvetenskaper/Diagnostisk radiologi
Angelina Bernardi1, Annica Andersson1, Louise Grahnemo 1,
Merja Nurkkala-Karlsson1, Hans Carlsten1, Ulrika Islander1
Abstractnummer: 40
1
Göteborgs Universitet
Background/Aim
Lasofoxifene (las) and bazedoxifene (bza) are selective estrogen
receptor modulators (SERM) approved for the prevention and
treatment of postmenopausal osteoporosis. 17β-estradiol (E2)
and the traditional SERM raloxifene (ral) both have antiarthritic
and bone protective properties in experimental postmenopausal
arthritis. Preliminary data from our ongoing studies show that treatment with las and bza significantly inhibits experimental arthritis and inflammation-induced bone loss. In order to understand the
mechanism for the beneficial effect of las and bza on arthritis it is
necessary to clarify how they affect the healthy immune system.
The inhibitory effect of E2 on B lymphopoesis and stimulatory
effect on antibody production are well documented. However the
impact of las and bza on B cell development and function has never
previously been studied.
Materials/Methods
Healthy mice were ovariectomized (ovx). Mice received treatment
40
The Diagnostic Utility of Fluore-scence Optical Imaging in the Identification of Synovial Inflammation in
Hand and Wrist Joints.
Yogan Kisten, Noémi Győri MD, Ronald van Vollenhoven MD
PhD, Hamed Rezaei MD, Erik af Klint MD PhD, Carolina Romanus, Anna Karlsson
Background
Fluorescence optical imaging (FOI, “Rheumascan”) is a novel modality that allows imaging of inflammation in the hands using a fluorescent dye. Here, the utility of FOI in identifying synovitis was
compared to clinical examination and ultrasound (US).
Methods
A total of 748 joints of the bilateral hands and wrists, including 3
wrist joints, 5 MCPs, 5 PIPs, and 4 DIPs in 22 patients with inflammatory arthritis were examined clinically, by US and FOI.
Results
71 out of 748 joints (9%) were considered inflamed clinically, 139
27
ABSTRACTS
(19%) by US, and 123 (17%) by FOI. Of the clinically inflamed joints,
49 (69%) were inflamed by ultrasound, and 30/65 (46%) of these
joints were inflamed by FOI. 593/683 (87%) of joints that were clinically negative were negative by ultrasound and 590 (86%) were
negative by FOI. The agreement between clinical examination and
US was fair (kappa 0.39+0.05) and somewhat stronger than the agreement between clinical examination and FOI (kappa 0.23+0.05).
98/142 (69%) joints that were inflamed by US showed inflammation by FOI, while 576/606 (95%) non-inflamed joints by US were
non-inflamed by FOI. The agreement between US and FOI was
good (kappa 0.67+0.04). 27/30 (90%) joints that were inflamed
both by clinical examination and by US were inflamed by FOI.
Conclusions
The sensitivity of FOI for inflammation is 46-90%, and the specificity 86-95%, suggesting that it has lower sensitivity but similar
specificity compared to US. These findings suggest that FOI may be
used in practice as a complement to clinical examination, in particular when US is not available, in order to identify synovitis earlier
and with greater confidence.
Abstractnummer: 41
41
The Utility of Fluorescence Optical Imaging for
Detecting Clinically Silent Synovitis of the Hands
and Wrists.
Yogan Kisten, Noémi Győri MD, Ronald van Vollenhoven MD
PhD, Erik af Klint MD PhD, Hamed Rezaei MD, Anna Karlsson,
Carolina Romanus
Background
Fluorescence optical imaging (FOI, “Rheumascan”) is a novel modality that allows imaging of inflammation in the hands and wrists
using a fluorescent dye. Here, we investigated whether FOI could
be used for ascertaining subclinical synovitis.
Methods
A total of 748 joints of the bilateral hands and wrists, including
3 wrist joints, 5 MCPs, 5 PIPs, and 4 DIPs in 22 patients with inflammatory arthritis (RA: 9; JIA, gout, psoriatic arthritis, SLE, and
other diagnoses, 1-2 each) were examined clinically, by ultrasound
(US) and FOI. Joints were considered clinically inflamed when
both swollen and tender, and non-inflamed otherwise.
Ultrasound was considered positive for synovitis if both thickening on grey scale and Doppler signal were present. FOI was considered positive by visual inspection of the images.
Results
Out of 748 joints, 71 (9%) were considered inflamed by clinical examination and 677 were not. Of the clinically noninflamed joints,
100 were inflamed by US. Of these joints, 80 were inflamed by
FOI and 20 were not. Thus, the sensitivity of FOI for detecting
sub-clinical synovitis when defined as a positive US in the absence
of clinical inflammation was 80%. Out of the 577 joints that were
non-inflamed clinically and non-inflamed by ultrasound, 26 had inflammation by FOI, yielding a specificity of 95%.
Conclusion
Under the assumption that US can correctly identify sub-clinical
synovitis in clinically non-inflamed joints the sensitivity of FOI for
detecting subclinical synovitis in the hands and wrists is 80% and
the specificity 95%. These metrics suggest that it may be a useful
tool in the setting of identifying patients with very early synovial
inflammation of the hands/wrists.
28
Abstractnummer: 42
42
HÖFTFRAKTURER OCH INFLAMMATORISK REUMATISK SJUKDOM DALARNA 2001 -2011
Britt-Marie Nyhäll-Wåhlin
Bakgrund
Under de senaste 20 åren har patienter med höftfraktur alltmer
uppmärksammats. Bakomliggande orsaker till frakturerna är
främst ålder och osteoporos. Ytterligare en bidragande orsak kan
vara inflammatorisk reumatisk sjukdom. Samtidigt har man under
denna tid börjat använda potenta läkemedel för såväl osteoporos
som inflammatorisk reumatisk sjukdom.
Syfte
Beskriva förekomsten av höftfrakturer och höftfrakturer + inflammatorisk reumatisk sjukdom under 11 år (2001-2011) i Dalarna.
Material och metod
Patienter boende i Dalarna med höftfraktur, som vårdats inneliggande på ortopedkliniken (ortopeden Falun och Mora) under diagnoserna (förstagångsdiagnos) 720, 721 och 722 under åren 2001
– 2011 identifierades. Därefter adderades diagnoser för inflammatorisk reumatisk sjukdom från reumatologklinikens besöksregister.
Patienterna subgrupperades i frakturår, dvs 11 grupper och jämfördes med avseende på frakturantal, medelålder, kön och förekomst
av diagnos för inflammatorisk reumatisk sjukdom.
Resultat
5 907 patienter med förstagångshöftfraktur kunde identifieras; 1
842 män och 4 065 kvinnor (31% vs 69%). Äldsta patienten var 106
år, den yngsta 46 år. Medelåldern var 82 år (män 80 år, kvinnor 82
år). 209 höftfrakturpatienter (3,5%) hade en diagnos förenlig med
inflammatorisk reumatisk sjukdom (182 artritsjukdom, 27 systemsjukdom). I de 11 subgrupperna baserade på frakturår sågs en
minskning av antalet höftfrakturer (2001:572, 2006:540, 2011:524).
Antalet patienter med inflammatorisk artritdiagnos var få
(2001:18, 2006:19, 2011:13).
Slutsats
En trend till minskat antal höftfrakturer kan ses, men ingen skillnad i könsfördelning eller ålder vid fraktur. Även en viss trend till
färre patienter med inflammatorisk ledsjukdom kan anas, men det
krävs betydligt större patientmaterial med inflammatorisk ledsjukdom för att undersöka detta liksom för att se om höftfraktur är vanligare i denna grupp.
Abstractnummer: 43
43
VITAMIN D INSUFFISCIENCY OBSERVED IN 50-75% OF HEALTHY SWEDISH ADULTS
Eva Klingberg1, Göran Oleröd2, Ola Hammarsten2
1
Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden 2 Department of Clinical Chemistry and
Transfusion Medicine University of Gothenburg, Sweden
Background
Numerous observational studies associate vitamin-D insufficiency
(VDI) with chronic illnesses, including rheumatic diseases. There
are two definitions of VDI; serum 25-hydroxy vitamin-D (S-25OHD) <50nmol/L or <75nmol/L. We aimed to study the inter- and
intra-individual variations in S-25-OHD during different seasons
of the year and to explore demographic and lifestyle related para-
ABSTRACTS
meters associated with S-25-OHD in healthy Swedish adults.
Methods
Blood donor serum was collected during 12 months and analyzed
for 25-OHD and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin-D supplements,
smoking, physical activity, solarium use and sun holidays. To study the intra-individual variations in S-25-OHD repeated samples
were also collected from thrombocyte donors during a period from
April to November.
Results
540 blood donors (60% men; mean age 41±13 years) and 75 thrombocyte donors (92% men, aged 46±11 years) were included. S-25OHD varied greatly over the year correlating with the UV-B iirradiation intensity (rS=0.326;p<0.001).The mean S-25-OHD was
73% higher in July (81.9±26.2 nmol/L) than in February (47.4±20.7
nmol/L;p<0.001) During Jan-Mars S-25-OHD below the thresholds
of 50 and 75 nmol/L was observed in 58% and 88% respectively and
during July-September in 11% and 50% (p<0.001). S-25-OHD correlated negatively with BMI and S-iPTH, but was significantly higher in sun-holiday travellers, solarium-users, nonsmokers and in
the physically active. The intra-individual analyses showed a mean
increase in S-25-OHD of 8nmol/L/month between April to August
and that 27% of the subjects with a S-25-OHD <50nmol/L in late
spring remained at this level during the whole summer.
Conclusions
Vitamin-D insufficiency is common in the Swedish healthy adult
population. Approximately 75% had serum 25-OHD values <75
nmol/L during the whole year and 50% had serum 25-OHD values
<50 nmol/L during 50% of the year. Serum 25-OHD was strongly
associated with parameters related to sun exposure, but only weakly with intake of vitamin-D supplements.
Abstractnummer: 44
44
GLUCOCORTICOIDS PROTECT AGAINST TRABECULAR BONE
LOSS IN OVARIEC-TOMIZED MICE
Louise Grahnemo1, Caroline Jochems1,3, Annica Andersson1,
Cecilia Engdahl2, Marie K Lagerquist2, Claes Ohlsson2, Ulrika
Islander1, Hans Carlsten1
Centre for Bone and Arthritis Research (CBAR), Department of
Rheumatology and Inflammation research, The Sahlgrenska Academy, University of Gothenburg, Sweden. 2 Centre for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, The Sahlgrenska Academy,University of Gothenburg,
Sweden. 3 Laboratory of Tumor Immunology and Biology, Center for
Cancer Research, National Cancer Institute, National Institutes of
Health, Bethesda, MD, USA
1
Abstractnummer: 45
45
HEPATOCYTE GROWTH FACTOR, A NEW BIOMARKER FOR
OSTEOPROLIFERATION IN MALE AS PATIENTS?
Eva Klingberg, Merja Nurkkala, Hans Carlsten, Helena Forsblad-d’Elia
Institution of Medicine, Center for Bone and Arthritis Research 2
Department of Rheumatology and Inflammation Research, University of Gothenburg, Sweden
Background
Ankylosing spondylitis (AS) is characterized by osteoproliferation,
which can be seen as an enhanced reparative response to inflammation, mechanical stress or micro-damage. Male sex is a risk
factor for the disease and for the osteoproliferation.
Hepatocyte growth factor (HGF), initially known as a mitogen for
hepatocytes, is an important factor for regeneration and repair in
many tissues. HGF is produced by osteoblasts, has receptors on osteoblasts and osteoclasts and stimulates both cell types.
The aims of this study were to compare the serum HGF levels in
AS patients with healthy controls and to explore the association
with disease activity, osteoproliferation and bone density.
Methods
Serum from AS patients (modified NY-criteria) and healthy controls was analyzed for HGF with ELISA (Quantikine R&DSystems). Disease activity was assessed by BASDAI, ASDAS, ESR and
CRP, back-mobility with BASMI, syndesmophyte formation with
mSASSS and BMD with DXA of femoral neck.
Results
204 AS patients (87 women/117 men; age 50±13 years; symptom
duration 24±13 years; BASDAI 3.6±2.1; ASDAS-CRP 2.4±0.9) and
80 sex and age-matched controls were included. HGF was significantly higher in the AS patients compared with the controls (1556±452
vs. 1450±527 pg/ml p=0.024). HGF correlated with age in the male
AS patients (rS=0.316;p=0.001) but not in the female patients nor in
controls of both sexes. In the AS men HGF also correlated with ESR(rS=0.380;p<0.001), CRP(rS=0.304;p=0.001), BASMI(rS=0.323;p
<0.001), mSASSS (rS=0.302;p=0.001) and femoral neck
BMD(rS=-0.211;p=0.022), but in the female patients only with
ESR. HGF was significantly higher in male smokers (p=0.005),
although there was no age-difference in male smokers and
non-smokers. In multiple linear regression age, CRP, and smoking
were all independently associated with HGF.
Conclusion
Known risk factors for osteoproliferation in AS were independently associated with serum HGF. HGF could be a negative prognostic
biomarker, especially for the male AS patients. Further prospective
studies are warranted.
Abstractnummer: 46
46
Reactive oxygen species are diSpensable for ovariectomy-induced bone loss
Alexandra Stubelius1, Annica Andersson1, Rikard Holmdahl2,
Claes Ohlsson 1, Ulrika Islander1, Hans Carlsten1
Centre for Bone and Arthritis Research, Sahlgrenska Academy, Gothenburg University 2 Medical Inflammation Research, Karolinska
Institute
1
Abstractnummer: 47
47
S-CALPROTECTIN – A POTENTIAL MARKER OF INFLAMMATION
IN PATIENTS WITH PSORIATIC ARTHRITIS?
Claes Hansson, Med. stud1 Catharina Eriksson, MD, PhD2 GerdMarie Alenius, MD, PhD1
1
Department of Public Health and Clinical Medicine, Rheumatology,
Umeå University, Umeå, Sweden 2 Department of Clinical Microbiology/Clinical Immunology, Umeå University, Umeå, Sweden
1
29
ABSTRACTS
Abstractnummer: 48
48
FAECAL LEVELS OF CALPROTECTIN IN SYSTEMIC SCLEROSIS,
PRIMARY SJÖGREN’S SYNDROME AND RHEUMATOID
ARTHRITIS
Kristofer Andréasson1, Tore Saxne1, Agneta Scheja1, Izabela
Bartosik1, Thomas Mandl2, Roger Hesselstrand1
Institutionen för kliniska vetenskaper Lund, Avdelning för Reumatologi, Lunds Universitet 2 Institutionen för kliniska vetenskaper
Malmö, Avdelning för Reumatologi, Lunds Universitet
1
Abstractnummer: 49
49
THE INFANTILE GUT BACTERIAL COLONIZATION PATTERN IS
ASSOCIATED WITH HIGHER CYTOKINE RESPONSES BUT NOT
WITH THE PROPORTIONS OF REGULATORY T CELLS IN CHILDHOOD
Anna Rudin1, Hardis Rabe1, Anna Strömbeck1, Annica Ljung2,
Anna-Carin Lundell1, Kerstin Andersson1, Agnes Wold2, Ingegerd Adlerberth2
Avd för Reumatologi och Inflammationsforskning, Sahlgrenska Akademin 2 Avd för infektionssjukdomar, Sahlgrenska Akademin
Results
In total, we identified 394 singleton deliveries among women with a
history of a diagnosis of AS, and 1201 deliveries among the matched
general population controls.
Caesarean section and epidural analgesia was more common and
pregnancies tended to be of shorter gestational age. Adjustment for
maternal age, smoking habits, BMI and educational level did not
change point estimates of relative risk. Sensitivity analyses restricted to those with a diagnoses before start of gestation and exploring
effects in different calendar time periods resulted in similar point
estimates.
Conclusion
Women with AS had increased risk of being delivered with and
caesarean section, both planned and acute.
Abstractnummer: 51
51
PATIENTS WITH NON-AS AXIAL SPA AND AS HAVE SIMILAR
PREVALENCE AND LEVELS OF PATIENT REPORTED OUTCOME
MEASURES. RESULTS FROM A POPULATION BASED STUDY.
U Lindström1, A Bremander2, S Bergman2, E Haglund2, IF Petersson3, LTH Jacobsson1
1
Abstractnummer: 50
50
PREGNANCY OUTCOME IN PATIENTS WITH ANKYLOSING
SPONDYLITIS – A NATIONAL REGISTER STUDY
Gustav Jakobsson1, Olof Stephansson2, Johan Askling3,4, Lennart Jacobsson1
2
Department of Women and Child Health, Division of Obstetrics and
Gynecology, Karolinska Institutet, Stockholm, Sweden 3 Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 4 Dept of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
Dpt. Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Sweden 2 Clinical Sciences Lund,
Section of Rheumatology, Lund University, Sweden 3 Orthopedics,
Clinical Sciences, Lund University, Lund, Sweden
1
Background
Non-radiographic axial spondyloarthritis (nrax-SpA) is emerging as
a treatable disease comparable to ankylosing spondylitis (AS). The
aim of this study was to estimate the prevalence of nrax-SpA and compare the patient reported outcome measures (PROMS) to that of AS.
1
Background and aim
AS often starts in fertile age and is characterized by back pain, local
and systemic inflammation, and may require systemic treatment.
Other chronic inflammatory diseases, such as inflammatory bowel
disease and rheumatoid arthritis affect pregnancy and birth outcomes, but for AS this has not been studied, which was the aim of
this study.
Methods
We performed a, nationwide, registry- and population-based care-control study. Cases were identified by diagnosis of an ICD code
for AS in the Swedish national patient register at a visit to a specialist in rheumatology or internal medicine. For each index case 5
controls were identified matched for birth year, time and county
at first AS diagnosis. Data on cases and controls were linked to the
Medical Birth Register (MBR) for identification of pregnancy and
birth outcomes and to Statistics Sweden (educational level). Cases
and matched controls were included in the present analyses if they
had their first singleton birth after inclusion, i.e after diagnoses of
AS for cases. Relative risks were assessed using conditional logistic
regression models.
30
Methods
All health care seeking individuals, ≥18 years, given a SpA-diagnosis, according to ICD-10, (N = 5771), 2003 - 2007, were identified through the regional health care register in Skåne. 2009 they
were sent a questionnaire (response rate 48%), including questions concerning the SpA-features constituting the ASAS-criteria,
PROMS and medication. Review of clinical records support the notion of using AS as a substitute for radiographic changes. Non-AS
axial SpA was defined as having an ICD10 code of SPA without
having one of AS, and > 3 months of Back Pain (BP) the last year
and ≥2 SpA-features. Assuming similar answers from the nonresponders, prevalence rates were estimated for non-AS axial SpA and AS.
Results
742 responders had an AS-diagnosis (60.5% men) and 640 fulfilled
the study criteria for non-AS axial SpA (29.5% men). The prevalence of AS was 0.13% (95% CI; 0.115-0.148) and of non-AS axial SpA
0.11% (95% CI; 0.096-0.130). Mean values for PROMs and frequency of comorbidities were higher in the non-AS axial SpA vs both
the AS, and the subgroup of AS individuals reporting BP > 3months
during the last year. Self-reported present use of TNF-inhibitors
was similar between the groups (Table 1).
Conclusion
The results suggest that at a population level the prevalence for
non-AS axial SpA almost equals that for AS, but with a reverse gender distribution. The non-AS axial SpA group report similar frequencies of SpA- comorbidities (except psoriasis) and treatment with
TNF-inhibitors, but worse levels of perceived health.
ABSTRACTS
Abstractnummer: 52
52
Patienter med tidig axial spondylartrit inkluderade
i SPACE i Sverige har en hög förekomst av inflammation enligt MRI och kliniskt aktiv sjukdom
Sofia Exarchou 3, Christopher Schaufelberger1, Tomas Husmark 2, Joaquin Lopis 4, Per Larsson 5, Milad Rizk 6, Åke Thörner 7, Käth Nilsson 3, Carl Turesson 3, Lennart Jacobsson1
Avdelningen för reumatologi och inflammationsforskning, Sahlgrenska Akademin, Göteborgs Universitet, Göteborg 2 Reumatologiska kliniken, Falu lasarett, Falun 3 Reumatologiska kliniken, SUS,
Malmö 4 Sektionen för reumatologi, Skövde sjukhus 5 Reumatologiska kliniken, Karolinska sjukhuset, Stockholm 6 Reumatologiska kliniken, Västmanlands sjukhus, Västerås 7 Reumatologiska kliniken,
Eskilstuna sjukhus, Eskilstuna
1
Bakgrund
Relativt litet är känt om långtidsförlopp och prognostiska faktorer
för patienter med tidig axial Spondylartrit (ax-SPA).
Syfte
Att belysa långtidsförlopp och prognostiska faktorer för kronisk
sjukdom samt strukturella förändringar (ankyloserande spondylit
(AS) enligt New York kriterierna) vid ax-SPA.
Metod
Internationell multiccenter kohortstudie (SPondylArthitis Caught
Early (SPACE)) med centra i Holland, Norge och Italien. Patienter
identifierade i rutinsjukvård med följande inklusionskriterier;
1) ryggsmärta under 2 års duration, 2) 16 – 45 års ålder vid smärtdebut, 3) andra tecken talande för ax-SPA; minst 1 av tungt vägande
indikatorer (HLA-B27, MRI (ödem)/röntgen (bilateralt sakroiliit),
hereditet, uveit) eller minst 2 av andra mindre tungt vägande indikatorer (se figur nedan).
Patienterna följs kliniskt (vid inklusion, efter 3 mån och därefter
årligen) med frågeformulär, klinisk undersökning och provtagning,
samt med bilddiagnostik (röntgen och MRI av bäckenleder och
kotpelare) vartannat år.
Resultat
I december 2013 hade över 300 patienter inkluderats internationellt, varav 47 i Sverige . Bland de svenska patienterna (56% män)
var medelåldern vid symptomdebut 26 år, och medeldurationen
av ryggsmärta var 13 månader. Vid inklusion hade patienterna en
hög förekomst av HLA-B27 (94%) positivitet och inflammation av
bäckenleder enligt MRI (63%) (figur). PLATS FÖR FIGUR!
Vid inklusion behandlades 80% med NSAID, 10% med kortison
och 3% med TNF-hämmare. Genomsnittsliga värden (SD) för BASDAI respektive BASFI var 4,4 (1,9) och 2,2 (1,9).
Konklusion
Patienterna med tidig ax-SPA i svenska delen av SPACE har vid
inklusion en hög förekomst av inflammation enligt MRI samt sjukdomsaktivitet (BASDAI) som är jämförbara med studier av etablerad AS från t.ex. den Skånska kohorten SPAScania1. Studier av tidig
SPA har hög potential för att bidra till framtida kvalitetsförbättring
och forskning. 1. Haglund E, Bremander AB, Petersson IF et al. Prevalence of spondyloarthritis and its subtypes in southern Sweden.
Referens: Ann Rheum. Dis. 2011 Jun; 70(6):943-8.
Abstractnummer: 53
53
DIFFERENCES IN SPINAL MOBILITY MEASURES IN RELATION TO DISEASE DURATION AND BETWEEN SUBGROUPS
WITH AXIAL SPONDYLOARTHRITIS
Elisabeth Mogard2, Elisabet Lindqvist1, Stefan Bergman1,Ann
Bremander2 1 SRF 2 SWEREFO
Introduction
Spinal mobility is a core domain for research and clinical practice
in Ankylosing Spondylitis (AS) but less studied in undifferentiated
SpA (USpA). Our objective was to study the change of commonly
used spinal mobility measures stratified on disease duration in patients with AS and differences in these measures in AS vs. USpA.
Methods
Patients with AS or USpA were identified from a cohort attending a
specialist clinic. A cross sectional study, were the first measures of
spinal mobility for each patient recorded during 1999 to 2012 were
analyzed. Disease duration was split into tertiles, (<17 years (G1),
18-30 years (G2) and >31 years (G3)). Differences between AS G1/
G2/G3 were calculated with Kruskal-Wallis. Differences between
AS and USpA were controlled for sex and disease duration (ANCOVA).
Results
126 patients with AS vs. 57 with USpA were included in the study,
mean (SD) age 48.4 (13.7) vs. 41.6 (11.4) years and 23% vs. 46% were
women. In AS, lumbar, and thoracic measures, vital capacity and
the BASMI composite score were the first measures to deteriorate
in relation to disease duration (G1 vs. G2, p<0.035). Late in the disease all measures had deteriorated (G1 vs. G3, p<0.036). Patients
with USpA presented better scores in lumbar, hip and thoracic spinal measures (p<0.05), data controlled for sex and disease duration. In early disease (<17 years) also cervical measures (p<0.05)
were less affected compared to patients with AS.
Conclusion
The first measures to significantly change during the disease course in AS were the lumbar and thoracic mobility measures and the
BASMI score. As expected, patients with USpA were less affected
in mobility than patients with AS.
Keywords
Ankylosing spondylitis (AS), physical therapy, range of motion and
Spondyloarthritis
Abstractnummer: 54
54
Inflammatory Bowel Disease associated Arthritis
(IBD-aA): validity of diagnoses based on ICD-coding
and characteristics of the disease.
Panagiota Drivelegka1, Nikolaos Papachrysos2, Ingemar Petersson3, Ann Bremander4, Lennart Jacobsson1
2
Department of Gastroenterology, Sahlgrenska University Hospital/
Östra, Gothenburg, Sweden 3 Department of Orthopedics, Department of Clinical Sciences, Lund, Lund University, Lund, Sweden 4 Research and Development Centre, Spenshult Hospital for Rheumatic
Diseases, Halmstad, Sweden
1
Abstractnummer: 55
55
TRANSCRIPTIONAL ACTIVITY OF ADIPOSE TISSUE MAY BE AN
EARLY MARKER OF CARDIOVASCULAR RISK IN RHEUMATOID
ARHTRITIS
31
ABSTRACTS
Mitra Nadali 1, Rille Pullerits1, Karin Andersson1, Sofia Töyrä
Silfverswärd1, Maria Bokarewa1
FIVE YEARS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS
Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Gothenburg
Anna Södergren1, Kjell Karp2, Elisabet Lundström2, Torgny
Smedby3, Bozena Möller4, Solbritt Rantapää-Dahlqvist1, Solveig Wållberg-Jonsson1
1
Abstractnummer: 56
56
PREDICTION OF CORONARY ARTERY CALCIFICATION AND
RELATION TO INFLAMMATION IN RHEUMATOiD ARTHRITIS:
A FOLLOW-UP STUDY
Bengt Wahlin1, Thomas Meedt1, Fredrik Jonsson2, Michael
Henein2, Kjell Karp3, Solveig Wållberg Jonsson1
Enheten för folkhälsa och klinisk medicin, reumatologi, Umeå universitet 2 Enheten för folkhälsa och klinisk medicin, Umeå universitet
3
Enheten för kirurgisk och perioperativ vetenskap, klinisk fysiologi,
Umeå universitet
1
Background
We previously reported increased prevalence of coronary atherosclerosis in patients with RA. In this follow-up, we evaluated the
relation between measures of atherosclerosis, inflammatory markers and potential biomarkers of atherosclerosis at baseline and
the presence of coronary artery calcification (CAC) 12 years later.
Methods
Twenty-two RA patients (4m, 18f, mean age 65 years, RA-duration
30-36 years) from an original (baseline; n=39) ultrasound study of
atherosclerosis (intima-media-thickness (IMT) and plaque) were
included in this follow-up study 12 years after baseline. CAC was
assessed by CT and quantified according to Agatston. At the same
time, inflammatory markers (ESR, CRP, haptoglobin), clinical disease activity ( joint counts, DAS28, HAQ, VAS-scales) and lipids
(cholesterol, HDL, LDL, triglycerides) were measured. The effect
on CAC of cytokines (IL-6, IL2sR), adhesion molecules (ICAM-1,
sE-selectine), hemostatic factors (PAI-1, tPA-ag, vWF, fibrinogen,
D-dimer, cardiolipin antibodies), circulating immune complexes
and antibodies against modified LDL, all collected at baseline, was
also evaluated. Statistical analysis of factors explaining presence of CAC was done by orthogonal projection to latent structures
(OPLS) with repeated exclusion of variables without explanatory
information.
Results
Eight patients had no detectable CAC, 2 patients had CAC 1-10
and 12 had >10 (range 18-1700). The final OPLS model discriminated well between groups with low (0-10) and high CAC (>10),
predicting 68% and explaining 88% of the variation. ROC analysis showed 89% sensitivity and 92% specificity distinguishing high
CAC from low. The most important variables in the OPLS model
were baseline values of plaque, IMT, HDL, age, hypertension, tPA
and current DAS28. Patients with high CAC differed from those
with low regarding ESR (24,3 vs 9,9 mm/h; p<0.01) and swollen
joint count (2 vs 0; p<0,05).
Conclusion
In patients with long term RA, CAC was predicted by markers of endothelial activation and traditional cardiovascular risk factors, but
also current disease activity. These findings highlight the importance of inflammation in the process of atherosclerosis.
Abstractnummer: 57
57
PROGRESSION OF SUBCLINICAL ATHEROSCLEROSIS OVER
32
Inst för folkhälsa och klinisk medicin, enh för reumatologi, Umeå
universitet 2 Inst för kirurgi och perioperativ vetenskap, klinisk fysiologi, Umeå universitet 3 Enh för reumatologi, Östersunds sjukhus 4
Enh för reumatologi, Sunderby sjukhus
1
Background
In patients with rheumatoid arthritis (RA) of recent onset, we have
found intima media thickness (IMT) and flowmediated dilation
(FMD) to be similar as in controls. In this prospective 5-year follow
up, we investigated the progression of atherosclerosis, in relation
with traditional cardiovascular disease (CVD) risk factors and inflammation, in patients with early RA compared to controls.
Methods
Patients from northern Sweden diagnosed with early RA are
consecutively recruited into an ongoing prospective study. From
these, a subgroup aged ≤60 years (n=71) was consecutively included for ultrasound measurements of IMT of a. carotis communis
and FMD of a. brachialis at inclusion (T0) and after 5 years (T5).
40 age-sex-matched controls were included. The patients were clinically assessed and DAS28 was calculated as a composite measure
of RA disease activity. Blood was analysed for lipids, ESR and CRP.
Results
Patients with RA had a significant aggravation in both IMT (0.52
at T0 and 0.58 at T5, p<0.001) and FMD (109.2% at T0 and 107.0
at T5, p<0.001). In controls the increase was only significant for
IMT (0.55 at T0 and 0.60 at T5, p<0.001). In simple linear regression analyses among RA-patients, the IMT at T5 was significantly associated with several variables at T0: systolic blood pressure,
cholesterol, triglycerides, SCORE and Reynolds Risk Score. In the
corresponding analyses of FMD at T5, it was significantly inversely associated with age, smoking, SCORE as well as Reynolds Risk
Score at T0 and area under the curve (AUC) for DAS28 over 60
months.
Conclusions
After five years, the increase in subclinical atherosclerosis tended
to be more evident among patients with early RA compared to the
controls. Both traditional CVD risk factors as well as inflammatory
load over time seems to contribute to this increased atherosclerotic
findings among patients with RA.
Abstractnummer: 58
58
HJÄRT-KÄRLSJUKDOM VID PRIMÄRT SJÖGRENS SYNDROM EN PILOTSTUDIE
Linnea Signér1, Lilian Vasaitis1, Dag Leonard1, Lars Rönnblom1,
Elisabet Svenungsson, Gunnel Nordmark1
Reumatologsektionen, Institutionen för medicinska vetenskaper,
Uppsala Universitet, Uppsala 2 Reumatologsektionen, Institutionen för
medicin, Karolinska Sjukhuset och Karolinska Institutet, Stockholm
1
Bakgrund
Förekomsten av hjärt-kärlsjukdom vid primärt Sjögrens syndrom
(pSS) är ofullständigt studerad. Patienter med systemisk lupus erythematosus (SLE) har en ökad risk för hjärt-kärlsjukdom där en
ABSTRACTS
singelnukleotidpolymorfi (SNP) i signal transducer and activator
of transcription 4 (STAT4) är associerad med stroke (1). Syftet med
denna studie var att undersöka frekvensen hjärtkärlsjukdom hos
patienter med pSS, jämföra med SLE, analysera sambandet med
hög sjukdomsaktivitet vid diagnos mätt med European League
Against Rheumatism Sjögren´s syndrome disease activity index
(ESSDAI) samt studera associationen mellan hjärtkärlsjukdom och
STAT4.
ligast där genen NFKB1 kodar för p50 subenheten. Associationen
mellan en NFKB1 singelnukleotidpolymorfi (SNP) och patienter
med pSS positiva för SSA/SSB-antikroppar har beskrivits (2). En 4
baspar insertion/deletion (ins/del) -94ATTG, i promoterregionen
av NFKB1, har associerats till ulcerös kolit och försämrad överlevnad vid kolorektal cancer (3). Målet med denna studie var att analysera associationen mellan NFKB1 -94ATTG ins/del och pSS samt
anti-SSA/SSB-positivitet och kliniska manifestationer.
Material och metod
Totalt 114 patienter med pSS (90 % kvinnor, medelålder 60 år)
ingick i studien. Kliniska data insamlades från journalerna. Data
fanns tillgängliga för 170 patienter med SLE (88 % kvinnor, medelålder 51 år). STAT4 fanns genotypad hos 93 pSS patienter. Frekvenser jämfördes med Fishers exakta test, kontinuerliga variabler
med t-test eller Mann-Whitney U test och allelfrekvensen med associationsanalys.
Material och metod
Totalt 684 patienter med pSS (92,8 % kvinnor, medelålder 58 år,
73,8 % anti-SSA och/eller -SSB-positiva) från Sverige (n=488) och
Norge (n=196) och 1601 friska kontroller (Sverige n=1383, Norge
n=218) ingick i studien. NFKB1 -94ATTG ins/del genotypades med
TaqMan PCR (3). Insertionen (ins, 2xATTG) är vildtyp, deletionen
(del, 1xATTG) den mindre vanliga allelen. Associationsanalyser utfördes i PLINK. Kliniska data hämtades från journalerna.
Resultat
Tjugofem pSS patienter (21,9 %) hade haft en eller flera manifestationer av hjärt-kärlsjukdom (cerebrovaskulär sjukdom (CVS) 2,6
%, ischemisk hjärtsjukdom (IHS) 6,1 %, ischemisk perifer vaskulär
sjukdom 0 %, venös tromboembolism 8,8 % och engagemang av
hjärtklaffar 8,8 %). Frekvensen cerebrovaskulär sjukdom var lägre
än i SLE-gruppen (11,8 %, p=0,007). Det fanns ingen skillnad i sjukdomsaktivitet mätt med ESSDAI vid diagnos mellan pSS patienter
med och utan hjärt-kärlsjukdom.
Patienter med arteriell hjärt-kärlsjukdom (CVS+IHS) var äldre
och hade oftare antihypertensiv behandling jämfört med pSS utan
arteriell hjärtkärlsjukdom (p<0,01). En STAT4 SNP, rs7582694, var
associerad med arteriell hjärt-kärlsjukdom (p=0.03, odds ratio 3.0).
Resultat
Vi fann en association mellan NFKB1 -94ATTG del allelen och pSS
(allelfrekvens pSS 0,42, kontroller 0,38), p=0,01, OR 1,18.
Genotypen associerade i en dominant modell (del/del+del/ins
versus ins/ins) med p=0,02, OR 1,25. Samtliga patienter och 979
kontroller var tidigare genotypade för NFKB1 SNP rs4648022 (2).
En haplotyp av NFKB1 -94ATTG del och SNP rs4648022 associerade med pSS, p=0,03, OR 1,35.
Vi fann ingen association mellan NFKB1 -94ATTG del och förekomsten av SSA/SSB, Raynaud, artrit, hudvaskulit, spottkörtelsvullnad, lymfadenopati, lymfom, hypotyreos, leukopeni, hypergammaglobulinemi eller germinalcentra i läppspottkörtelbiopsin.
Slutsats
Patienter med pSS har, trots högre medelålder, en lägre frekvens
cerebrovaskulär sjukdom än patienter med SLE. Sjukdomsaktiviteten vid diagnos tycks inte bidra till hjärt-kärlsjukdom medan det
kan finnas en genetisk bakgrund till arteriell hjärtkärlsjukdom vid
pSS.
Referens
1. Svenungsson E et al. Ann Rheum Dis 2010; 69: 834-840.
Abstractnummer: 59
59
ASSOCIATION MELLAN NFKB1 -94ATTG INS/DEL PROMOTER
POLYMORFI OCH PRIMÄRT SJÖGRENS SYNDROM
Gunnel Nordmark1, Lilian Vasaitis1, Elke Theander2, Marika
Kvarnström3, Christopher Sjöwall4, Helena Forsblad-d´Elia5,
Helmi Jazebi3,6, Marie Wahren-Herlenius3, Maija-Leena Eloranta1, Per Eriksson4
Reumatologsektionen, Institutionen för medicinska vetenskaper,
Uppsala universitet, Uppsala 2 Reumatologsektionen, Skånes universitetssjukhus Malmö, Lunds universitet, Malmö 3 Reumatologsektionen, Institutionen för medicin, Karolinska Institutet, Stockholm
4
Reumatologsektionen, Institutionen för klinisk och experimentell
medicin, Linköpings universitet, Linköping 5 Avdelningen för reumatologi och inflammationsforskning, Sahlgrenska akademin, Göteborgs universitet, Göteborg 6 Reumatologsektionen, Universitetssjukhuset Örebro, Örebro
1
Bakgrund
Aktivering av NF-kappaB resulterar i inflammation och autoimmunitet och har visats i salivkörtelepitelceller från patienter med primärt Sjögrens syndrom (pSS) (1). Heterodimeren p50/p65 är van-
Slutsats
Genetisk variation i NFKB1 -94ATTG ins/del visas här för första
gången associerad med pSS. Hur denna genvariant påverkar aktiveringen av NF-kappaB vid pSS är okänt och mål för framtida studier.
Referenser
1 Lisi S et al. Laboratory investigation 2012
2 Nordmark G et al. Scand J Immunol 2013
3 Ungerback J et al. Carcinogenesis 2012
Abstractnummer: 60
60
SERUM MEDIATED PHAGOCYTOSIS OF NECROTIC MATERIAL
BY POLYMORPHONUCLEAR LEUKOCYTES IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE).
Michele Compagno1, Birgitta Gullstrand2, Andreas Jönsen1,
Lennart Truedsson2, Gunnar Sturfelt1, Anders A. Bengtsson1
Institutionen för kliniska vetenskaper i Lund, Avdelningen för Reumatologi, Lunds Universitet 2 Institutionen för laboratoriemedicin i
Lund, Avdelningen för Mikrobiologi, Immunologi och Glykobiologi,
Lunds Universitet
1
Background
Polymorphonuclear (PMNs) leukocytes with engulfed necrotic
cell material (NCM), as formerly used in the LE-cell test, are frequently seen in SLE and associated to severe clinical manifestations.
The aim of this study was to investigate if phagocytosis of NCM
could predict or was associated with specific clinical phenotypes
and/or disease activity in patients affected by SLE.
Methods
Sixty-nine SLE-patients were followed longitudinally for a median
time of 2.1 years. A total of 1074 serum samples were taken approxReumaBulletinen Nr 96 · 2/2014
33
ABSTRACTS
imately every 60 days together with registration of an extensive set
of clinical and laboratory variables. NCM was generated by heat
treatment of mononuclear cells from healthy donors, and PMNs
from healthy donors were isolated by density gradient centrifugation. Sera from SLE-patients were incubated with PMNs and NCM,
and phagocytosis was assessed by flow cytometry. Association and
prediction of relevant clinical phenotypes and disease activity (measured by SLEDAI) were evaluated with mixed model and odds ratio (OR) and 95% confidence intervals (CI) were calculated.
Results
In serum samples from 46 of the 69 SLE patients, phagocytosis of
NCM by PMNs was seen at least once and totally 417 times.
Significant association between phagocytosis of NCM by PMNs
was found with clinical phenotypes such as lupus nephritis
(OR=1.7, CI=1.2-2.5), mucocutaneous involvement (OR=1.45, CI=1.11.9), arthritis (OR=0.51, CI=0.3-0.8) and also with increased SLEDAI (OR=1.41, CI=1.0-2.0). Furthermore, phagocytosis of NCM by
PMNs could predict alopecia (OR=2.22, CI=1.3-3.7) and was inversely related to arthritis (OR=0.38, CI=0.1-1).
Conclusion
In SLE, high capacity of serum mediated phagocytosis of NCM by
PMNs may be associated with certain clinical features (mucocutaneous and renal involvement) and disease activity. It may be a predictor for alopecia. It is inversely related to a milder disease course
(arthritis). Thus, its assessment may be used as a complementary
laboratory tool in SLE-patients.
Abstractnummer: 61
61
LOW PRODUCTION OF REACTIVE OXYGEN SPECIES IN GRANULOCYTES IS ASSOCIATED WITH ORGAN DAMAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS
Anders Bengtsson1, Åsa Pettersson2, Stina Wichert3, Birgitta
Gullstrand, Markus Hansson3, Thomas Hellmark2, Åsa Johansson3
Department of Clinical Sciences, Section of Rheumatology, Lund University and Skåne University Hospital, Sweden 2 Department of Nephrology, Clinical Sciences, Lund University, Lund, Sweden 3 Department
of Haematology, Lund University and Skåne University Hospital,
Sweden 4 Department of Laboratory medicine Lund. Section of Microbiology, immunology and Glycobiology, Lund University, Lund,
Sweden 5 Clinical Immunology and Transfusion Medicine, University
and Regional Laboratories Region Skåne, Lund, Sweden 2014
1
Abstractnummer: 62
62
ly been detected in SLE patients, their role in SLE pathogenesis
still remains elusive. The aim of this study was to evaluate levels of
anti-HMGB1 antibodies in relation to other autoantibodies and to
disease activity in a Swedish cohort of SLE patients.
Subjects and methods
Serum from 205 patients with SLE (92% female; mean age 50.5
years/range 18-80; mean duration 11 years/range 0-45) and from
112 healthy donors (91% female; mean age 46.5 years/range 19-84).
Levels of anti-HMGB1 antibodies were detected by ELISA. Briefly,
plates were coated with recombinant HIS-tagged HMGB1, blocked with milk and incubated with serum samples diluted 1:500.
HRP-conjugated anti-human IgG was added and after development, the absorbance was measured.
Arbitrary units (AU) were calculated by normalization against a
positive control sample. Cut-off value 300 AU was calculated as
mean value of the healthy controls + 2 standard deviations.
Results
22% of the SLE patients were anti-HMGB1 antibody positive compared to 4% of the healthy controls. The levels of anti-HMGB1 antibodies were significantly higher in the patients compared to the
healthy controls. The levels of anti-HMGB1 antibodies correlated
significantly with the levels of anti-dsDNA antibodies, SLE Disease
Activity Index (SLEDAI) and erythrocyte sedimentation rate, whereas albuminuria, complement function (classical pathway) and
complement protein C4 were inversely
correlated with anti-HMGB1.
Conclusion
The correlation of anti-HMGB1 antibodies with SLE disease activity scores and serological measures of disease activity indicates
that these antibodies may be involved in the pathogenesis of SLE.
Our findings also suggest that anti-HMGB1 antibodies may serve as
a useful diagnostic and prognostic tool in SLE.
Abstractnummer: 63
63
PLATELET ACTIVATION AND ANTIPHOSPHOLIPID ANTIBODIES COLLABORATE IN THE ACTIVATION OF THE COMPLEMENT
SYSTEM ON PLATELETS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Christian Lood1, Helena Tydén1, Birgitta Gullstrand2, Gunnar Sturfelt1, Andreas Jönsen1, Lennart Truedsson2, Anders
Bengtsson1
Department of Clinical Sciences Lund, Section of Rheumatology,
Lund University and Skåne University Hospital, Lund, Sweden 2 Department of Laboratory Medicine Lund, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund
1
64
EVALUATION OF AUTOANTIBODIES AGAINST HIGH MOBILITY
GROUP BOX PROTEIN 1 (HMGB1) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Abstractnummer: 64
Hanna Schierbeck1, Lina Wirestam2, Marie Fischer1, Lars Ottosson1, Ann-Charlotte Aveberger1, Christopher Sjöwall2, Jonas
Wetterö2, Erik Sundberg1, Thomas Skogh2, Helena Erlandsson
Harris1
EFFECT OF SINGLE-NUCLEOTIDE POLYMORPHISMS ON TYPE
I INTERFERON PRODUCTION BY PLASMACYTOID DENDRITIC
CELLS STIMULATED WITH SLE-ASSOCIATED IMMUNE COMPLEXES
1
Karolinska Institutet 2 Linköping University
Introduction
HMGB1 has been implicated in the pathogenesis of SLE since
HMGB1 is required in the DNA-containing immune complexes
that stimulate production of anti-dsDNA antibodies, which is a
hallmark of SLE. Although anti-HMGB1 antibodies have previous34
Olof Berggren1, Andrei Alexsson1, Karolina Tandre1, AnnChristine Syvänen2, Lars Rönnblom1, Maija-Leena Eloranta1
Uppsala University, Dept. of Medical Sciences, Rheumatology and
Science for Life Laboratory, Uppsala, Sweden. 2 Uppsala University,
Dept. of Medical Sciences, Molecular Medicine and Science for Life
Laboratory, Uppsala, Sweden.
1
ABSTRACTS
Introduction
Systemic lupus erythematosus (SLE) and many other systemic
autoimmune diseases have a persistently activated type I interferon (IFN) system, displayed as elevated serum levels of IFN-alpha
and increased expression of type I IFN inducible genes (an IFN
signature). Lately, studies have shown an association between the
susceptibility to SLE and several gene variants within the type I
IFN system, and we have showed that IFN-alpha production by the
plasmacytoid dendritic cell (pDC) was enhanced by crosstalk with
natural killer (NK) cells and B cells.
Laboratory, Uppsala University 2 Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural
Sciences
Aim
We investigated whether single nucleotide polymorphisms (SNPs)
associated with SLE and other autoimmune diseases have an impact on the IFN-alpha production by pDC. Methods: pDC, B and
NK cells were isolated from peripheral blood obtained from healthy individuals, and stimulated with RNA-containing immune complexes (IC), herpes simplex virus (HSV) or the oligonucleotide
ODN2216. IFN-alpha production was measured in the cell cultures
by an immunoassay. All blood donors were genotyped with 200K
ImmunoChip and a 5bp CGGGG length polymorphism in the IFN
regulatory factor 5 gene (IRF5) by PCR.
Methods
Human T cells were activated by anti-CD3/CD28 antibodies or in
a mixed leukocyte reaction (MLR). T cells or supernatant from T
cell cultures were co-cultured with pDCs stimulated with immune
complexes containing U1 snRNP particles and SLE-IgG (RNA-IC).
Cells were analyzed by flow cytometry and cytokines in co-culture
supernatants were depleted or blocked by monoclonal antibodies.
Culture supernatants were analyzed after 20h for IFNα and other
cytokines.
Results
We found associations between IFN-alpha production and 28-107
SNPs (p<0.001) depending on the combination of stimulated cell
types. However, only three of these associated SNPs were shared
between the cell type combinations. Several of the SNPs have not
been associated with type I IFN production previously, while some
loci have been described earlier for their genetic association with
SLE. Furthermore, we found that the SLE-risk variant of the 5 bp
IRF5 CGGGG-indel was associated with a lower IFN-alpha production.
Conclusion
We found a large number of genetic variants affecting the IC-mediated type I IFN production that highlight the intricate regulation
of the type I IFN system and can reveal new therapeutic targets
for SLE.
Abstractnummer: 65
65
TYPE I INTERFERON-MEDIATED DECREASE OF THE SEROTONIN
SYNTHESIS IN SYSTEMIC LUPUS ERYTHEMATOSUS – A POSSIBLE RELATION TO CARDIVASCULAR DISEASE?
Christian Lood1, Helena Tydén1, Birgitta Gullstrand, Cecilia
Klint, Christina Wenglén, Christoffer Nielsen, Niels Heegaard,
Andreas Jönsen1, Anders Bengtsson1
Department of Clinical Sciences Lund, Section of Rheumatology, Lund
University and Skåne University Hospital, Lund, Sweden 2 Department
of Laboratory Medicine Lund, Section of Microbiology, Immunology and
Glycobiology, Lund University, Lund, Sweden 3 Anamar AB, Lund,
Sweden 4 Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark
1
Abstractnummer: 66
66
Activated T-cells Enhance the Interferon-α Production by RNA-IC stimulated Plasmacytoid Dendritic Cells
Dag Leonard1, Maija-Leena Eloranta1, Niklas Hagberg1, Olof
Berggren1, Karolina Tandre1, Gunnar Alm2, Lars Rönnblom1
1
Department of Medical Sciences, Rheumatology, Science for Life
Background
A prominent interferon-α (IFNα) signature is seen in several autoimmune diseases, including systemic lupus erythematosus (SLE).
We asked if T cells can promote the IFNα production by plasmacytoid dendritic cells (pDCs) stimulated with RNA containing
immune complexes.
Results
Activated T cells or supernatants from activated T cells increased the IFNα production >20-fold. After addition of cytokines to
RNAIC stimulated pDCs, GM-CSF and IL-3 was demonstrated to
increase the IFNα production. This stimulatory effect was reduced
after depletion of GM-CSF in supernatants from activated T cells
(81%), blocking of GM-CSF (78%) or its receptor subunits CD131
and CD116 (70-75%). Supernatant from activated T cells also increased the frequency of CD80 and CD86 expressing RNA-IC stimulated pDC from 7% to 37% and 8% to 21%, respectively. Activated
SLE-T cells enhanced the IFNα production in RNA-IC stimulated
pDC to the same extent as activated T cells from healthy individuals. Elevated levels of serum-GM-CSF (4.2-128 pg/ml) was found in
30% of SLE patients, all characterized by increased levels of serum-IFNα (3.0-29 U/ml).
Conclusions
Activated T cells enhance the IFNα production by RNA-IC stimulated pDCs via GM-CSF and IL-3 and induces maturation of the
pDCs. The observation that all SLE patients with measurable serum levels of GM-CSF had elevated serum levels of IFNα indicates
that activated T cells may be important for the ongoing IFNα production in this disease.
Abstractnummer: 67
67
AUTOANTIBODIES TO THE CD94/NKG2A AND CD94/NKG2C
RECEPTORS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Niklas Hagberg1, Jakob Theorell2, Karin Hjorton1, Maija-Leena Eloranta1, Yenan Bryceson2,3, Lars Rönnblom1
Department of Medical Sciences, Section of Rheumatology, Science for Life Laboratories, Uppsala University 2 Center for Infectious
Medicine, Department of Medicine, Karolinska Institute, Karolinska
University Hospital Huddinge 3 Broegelmann Research Laboratory,
Institute for Clinical Sciences, University of Bergen
1
Introduction
Recently, we serendipitously identified a patient with SLE harboring autoantibodies to CD94/NKG2A.
CD94/NKG2A is a NK cell receptor that binds HLA-E and regulates cytotoxicity. In the present study, we investigated the occurrence and function of autoantibodies targeting the CD94/NKG2A,
35
30
ABSTRACTS
CD94/NKG2C or NKG2D receptors in patients with SLE.
Method
Sera from 203 SLE patients and 90 healthy individuals were analyzed for Ig-binding to murine Ba/F3 cells transfected with CD94/
NKG2A, CD94/NKG2C or NKG2D, using flow cytometry. Identified autoantibodies were characterized for interference with
HLA-E-binding, effect on NK cell degranulation in response to
HLA-E-transfected K562 cells, and their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC).
The exons encoding NKG2A (KLRC1), NKG2C (KLRC2), and
CD94 (KLRD1) were sequenced. The titers of anti-CD94/NKG2A
and anti-CD94/NKG2C autoantibodies were determined in longitudinally sampled sera and correlated to disease activity (SLEDAI)
and severity (SLICC/ACR damage index).
Results
Anti-CD94/NKG2A autoantibodies were detected in sera from
seven patients. Six sera inhibited HLA-E-binding to CD94/NKG2A, whereas one increased this binding. Two of these sera also
contained Ig that bound CD94/NKG2C, with one inhibiting, and
one augmenting, HLA-E-binding to CD94/NKG2C. Anti-CD94/
NKG2A and anti-CD94/NKG2C autoantibodies abrogated the
HLA-E-mediated inhibition of CD94/NKG2A+ and activation of
CD94/NKG2C+ NK cells, respectively. Furthermore, these autoantibodies facilitated elimination of CD94/NKG2A- and CD94/NKG2C-expressing cells through ADCC.
No unique nonsynonymous sequence variations were found in
KLRC1, KLRC2, or KLRCD1. The titers of anti-CD94/NKG2A autoantibodies were associated to disease activity.
Conclusions
Autoantibodies targeting the CD94/NKG2A or the CD94/NKG2C
receptor are found in a subset of patients with SLE. Their titers are
associated to the disease activity and a more severe SLE phenotype. Mechanistically, the autoantibodies can affect NK cell cytotoxicity and mediate ADCC. Consequently, anti-CD94/NKG2A and
anti-CD94/NKG2C autoantibodies may contribute to the pathogenesis of SLE and our findings highlight the possible importance of
NK cells in the SLE disease process.
Abstractnummer: 68
68
INTRATHECAL LEVELS OF SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS (SRAGE) IN PATIENTS WITH
SUSPECT NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS
Estelle Trysberg1, Sara Haghighi2, Rille Pullerits 1
Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg 2 Department of Neuroscience and Physiology, Institute of
Clinical Neuroscience, The Sahlgrenska Academy at the University
of Gothenburg
1
Abstractnummer: 69
69
Pro-inflammatory S100 proteins are associated
with glomerulonephritis and anti-dsDNA antibodies
in systemic lupus erythematosus
Helena Tydén1, Christian Lood1,2, Birgitta Gullstrand2, Andreas Jönsen1, Fredrik Ivars3, Tomas Leanderson3, Anders A
Bengtsson1
Department of Clinical Sciences, Division of Rheumatology, Lund
University and Skane University Hospital, Lund 2 Department of
Laboratory Medicine, Division of Microbiology, Immunology and
Glycobiology, Lund University, Lund 3 Department of Experimental
Medical Science, Immunology Group, Lund University, Lund
1
Background
Phagocytosis of autoantibody-coated necrotic cell material (NC) by
polymorphonuclear neutrophils (PMNs) is commonly seen in SLE
patients but downstream events such as PMN-mediated activation
and release of proinflammatory S100 proteins are less investigated.
We specifically wanted to know if S100A8/A9 and S100A12 serum
levels could be related to phagocytosis of NC by PMNs in vitro,
disease activity, as well as to the clinical phenotype in SLE.
Methods
Serum levels of S100A8/A9 and S100A12 from 100 SLE patients
were measured with ELISA. Phagocytosis of NC by PMNs from
healthy donors in the presence of SLE serum from the 100 SLE patients was analysed by flow cytometry. Disease manifestations and
autoantibody profile at the time point of blood sampling were also
recorded.
Results
Serum levels of S100A8/A9 and S100A12 were increased in SLE
patients with active disease as compared to healthy controls
(p<0.0001 and p=0.0001, respectively). S100A8/A9 serum levels
were particularly increased in SLE patients with anti-dsDNA antibodies (p=0.01), as well as in patients with serum with high ability
to support phagocytosis of NC by PMNs (p=0.01). Furthermore, increased serum levels of S100A8/A9 were seen in SLE patients with
active glomerulonephritis who had not started treatment with
immunosuppressive drugs (p=0.04) compared to patients at flare
without this manifestation.
Conclusions
Elevated serum levels of S100A8/A9 and S100A12 were seen in active SLE. The elevated serum levels of S100A8/A9 were associated
with glomerulonephritis, presence of anti-dsDNA antibodies and
a high capacity to promote phagocytosis of NC by PMNs. Serum
levels of S100A8/A9 and S100A12 may be useful markers of disease
activity in SLE patients.
Abstractnummer: 70
70
Comparison of three assays to assess antibodies
against double-stranded DNA in systemic lupus erythematosus
Helena Enocsson1, Lina Wirestam1, Charlotte Dahle2, Johan
Rönnelid3, Alf Kastbom1, Jonas Wetterö1, Christopher Sjöwall1, Thomas Skogh1
Rheumatology/AIR, Department of Clinical and Experimental
Medicine, Linköping University, Linköping, Sweden 2 Clinical Immunology & Transfusion Medicine, County Council of Östergötland,
Linköping Sweden 3 Genetics & Pathology, Department of Immunology, Rudbeck Laboratory C5, Uppsala University, Sweden
1
Background
Analysis of antibodies against double-stranded DNA (anti-dsDNA)
is a diagnostic tool in systemic lupus erythematosus (SLE). Generally, anti-dsDNA analyses by conventional enzyme-immunoassays
have lower diagnostic accuracy than the Crithidia luciliae immunofluorescence test (CLIFT) and Farr. Herein, CLIFT was used
37
ABSTRACTS
as reference to compare the PhaDia enzyme immunoassay and the
fluorescent microspehere immunodetection system (FIDIS).
Subjects and methods
Sera from 192 SLE patients were analyzed for IgG anti-dsDNA by
CLIFT (cut-off >99th percentile among 100 healthy female blood
donors), PhaDia (Thermo Fisher Scientific/Phadia AB) and FIDIS
(Theradiag) with the cut-off limits suggested by the manufacturers.
The patients were from the KLURING project (Kliniskt Lupusregister i nordöstra Götaland) and fulfilled the 1982 ACR criteria
(81%) or the Fries’ criteria. For CLIFT and PhaDia, the following
disease controls were included: 100 blood donors (50 women, 50
men), 97 with rheumatoid arthritis and 54 patients with primary
Sjögren’s syndrome.
Results
Phadia captured a higher number of SLE patients (34%) than
CLIFT (25%) but did also detect a higher number of disease controls. Fisher’s exact test revealed that all anti-dsDNA tests showed
significant positive associations to ACR criterion 7 (renal disease)
and 10 (immunologic disorder). CLIFT and FIDIS, but not PhaDia,
showed significant negative associations to criterion 3 (photosensitivity), whereas PhaDia alone showed a negative association to
criterion 4 (oral ulcers). Anti-dsDNA measured by CLIFT correlated more strongly to FIDIS (rho=0.631) than to PhaDia (rho=0.475).
The correlation coefficient between PhaDia and FIDIS was 0.607.
Conclusion
When CLIFT is chosen as ‘the gold standard’ for anti-dsDNA measurement in SLE, the present study indicates that FIDIS performs
better than PhaDia. This applies both to the associations with disease manifestations, and to correlation with CLIFT anti-dsDNA.
As regards diagnostic specificities, we found that a positive CLIFT
was more SLE-specific than PhaDia.
Abstractnummer: 71
71
Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus
Martina Frodlund1, Örjan Dahlström2, Alf Kastbom1, Thomas
Skogh1, Christopher Sjöwall1
Medicine, Linköping University, Linköping 2 Swedish Institute for
Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping
1
An abnormal antinuclear antibody (ANA) titer evaluated by immunofluorescence (IF) microscopy is a cornerstone in the 1982
American College of Rheumatology (ACR-82) classification criteria of systemic lupus erythematosus (SLE) as well as in the new
Systemic Lupus International Collaborating Clinics (SLICC) criteria. Several studies have addressed the clinical value of ANA finespecificities in SLE but, to our knowledge, has none evaluated
how distinct ANA staining patterns are related to clinical features
of SLE. Thus, we aimed at comparing indirect IF microscopy patterns with SLE phenotypes in a local Swedish SLE-register. 222
SLE patients taking part in the prospective control programme at
Linköping university Hospital. 178 patients (80%) met the ACR-82,
whereas 44 (20%) had a clinical SLE based on abnormal ANA titer
and ≥two typical manifestations (Fries criteria). ANA was analyzed
by IF microscopy using multispot slides with fixed HEp-2 cells,
anti-dsDNA by Crithidia luciliae and autoantibodies to extracta-
38
ble nuclear antigens by double radial immunodiffusion and/or line-blot. Differences in the proportions of patients with homogenous, speckled, homogenous/speckled and nucleolar±combination
with other patterns were calculated. 54% SLE patients displayed
homogenous staining, 22% speckled, 11% homogenous/speckled,
9% nucleolar±other patterns.
Homogenous staining pattern was associated with immunologic
disorder (p<0.001). Speckled pattern was inversely associated with
arthritis (p=0.02), immunologic disorder (p<0.001) and SLICC/
ACR damage index ≥1 (p=0.007). Positive anti-SSA antibody test
was associated with photosensitivity (p=0.023) and inversely associated with arthritis (p=0.016).
This cohort of well-characterized patients confirmed that homogenous nuclear staining is the most common IF-ANA pattern
in Caucasian SLE patients. The inverse relation between speckled pattern and arthritis was strengthened by the corresponding
relation between anti-SSA and arthritis. The previously described
association between anti-SSA and photosensitivity was confirmed.
The inverse relationship between speckled staining and SLICC/
ACR damage index could indicate a milder disease with a better
prognosis for individuals with this ANA pattern.
Abstractnummer: 72
72
Quality of life and organ damage are strongly related to activity limitations in patients with systemic lupus erythematosus
Mathilda Björk1, Örjan Dahlström2, Jonas Wetterö3, Christopher Sjöwall3
Rehabenheten HMC, Linköpings universitetssjukhus, Landstinget i
Östergötland 2 Institutionen för beteendevetenskap och lärande, Linköpings universitet 3 Avdelningen för reumatologi/AIR, IKE, Hälsouniversitetet i Linköping
1
Objective
Systemic lupus erythematosus (SLE) is an autoimmune multi-organ disease, characterized by episodes of disease flares and remissions over time, which may restrain affected patients’ ability
to perform daily activities. The aims of the present study were to
describe the variation in activity limitation among well-defined
SLE patients, and to identify the influence of disease phenotypes
on activity limitation and patient self-reported health.
Methods
The disease phenotypes were organized into 4 different clusters
and logistic regression analyses were used to identify how an elevated health assessment questionnaire (HAQ) score was related to
the phenotypes. Correlation and multiple linear regression
analyses were used to examine the association between each group
of variables – demographics, disease variables and self-reported
measurements – and the degree of elevated HAQ.
Results
We found a higher proportion of activity limitation in SLE patients
with skin and joint manifestations compared to others. The presence of activity limitation, as detected by the HAQ instrument,
was significantly associated with quality of life (EuroQol–5D) and
irreversible organ damage (SLE international collaborative clinics/
ACR damage index).
Conclusions
The findings highlight the differing requirements of the multi-professional rehabilitation interventions for the various SLE phenoty-
ABSTRACTS
pes in order to optimize the clinical care of the patients.
Abstractnummer: 73
73
SF-36 in SLE of Various Disease Durations: A comparison
with RA and controls
Christine Bengtsson1, Elias Jönsson2, Elisabet West3, Solveig
Wållberg-Jonsson4
Inst för Folkhälsa och Klinisk medicin, UMU. Reumatologenheten,
Östersunds sjukhus 2 Läkarstudent, T10, UMU 3 Reumatolokliniken,
NUS 4 Inst för Folkhälsa och Klinisk medicin, UMU
1
Objective
The aim of this study was to evaluate the self-experienced health
in patients with systemic lupus erythematosus (SLE) in relation to
patients with rheumatoid arthritis (RA) and controls. A further aim
was to compare the self-experienced health over time and between
sexes.
Method
Patients from the Northern region of Sweden with SLE; short (2
years) (n=17), medium (6 years) (n=46) and long (20 years) (n=47)
disease duration (DD), were compared with RA-patients (n=51, respectively 51 and 39) and healthy age- and sex matched controls
(n=36). Quality of life was measured using SF-36 health survey
consisting of eight domains; Physical Function (PF), Role Physical
(RP), Role Emotional (RE), Social Function (SF), Bodily Pain (BP),
Mental Health (MH), Vitality (VT), Global Health (GH) but is also
summarized into: physical (PCS)- and mental (MCS) component
summary.
Results
Lower quality of life was seen in all groups of DD in SLE compared
with RA. This was noted at 2 year regarding SF (p=0.04), 6 year regarding SF (p=0.01), MH (p=0.002), VT (p=0.02) and MCS (0.002)
and at 20 year regarding SF (p=0.003), VT (p=0.006), GH (p=0.012)
and MCS (p<0.001). The only domain where SLE- patients estimated their health higher than RA- patients was PF (p=0.019) at 20
years DD. Patients with SLE estimated their health significantly
lower regarding all domains compared with controls. This was also
noted regarding RA all DDs and controls except mental component
(p>0.17). In SLE men generally estimated their health higher compared with women in contrast with RA.
Conclusion
We found that the SLE-patients generally experienced lower quality of life than RA-patients. Especially noted in 20 years DD, where the SLE-patients scored significantly lower than RA-patients in
three domains and one dimension. Lower quality of life was noted
among women compared with men in SLE, at contrast with the
results in RA.
Abstractnummer: 74
74
UTILITY OF SWEDISH REGISTER DATA IN CLASSIFYING SYSTEMIC LUPUS
Elizabeth Arkema1, Andreas Jönsen2, Lars Rönnblom3, Christopher Sjöwall4, Elisabet Svenungsson, Julia Simard1,6,7
Karolinska Institutet, Department of Medicine, Clinical Epidemiology Unit 2 Lund University Hospital, Department of Rheumatology 3
Uppsala University, Department of Medical Sciences, Rheumatology
1
Unit 4 Linköping University, Dpeartment of Clinical and Experimental Medicine 5 Karolinska University Hospital, Department of Medicine, Rheumatology Unit 6 Stanford School of Medicine, Department
of Health Research and Policy, Division of Epidemiology 7 Stanford
School of Medicine, Department of Medicine, Division of Rheumatology and Immunology
Background
Systemic Lupus Erythematosis (SLE) is a rare disease, making it
a challenge to achieve an adequate sample size for many research
questions. Our aim was to use data mining techniques to identify
a classification algorithm using national register data in Sweden.
Methods
Clinically confirmed SLE cases were pooled from four major clinical centers in Sweden (Linköping, Lund, Stockholm and
Uppsala), we excluded cases with <4 ACR criteria. We identified a
population of non-SLE comparators by randomly selecting individuals from the National Population Register matched on age, sex
and county to individuals with SLE from the national registers.
Both cases (N=940) and comparators (N=24,370) were restricted
to adults (>16y) living in Sweden January 1, 2010. Covariates on demographics, comorbid conditions, prescriptions and family history
of autoimmune disease were obtained from multiple registers and
linked to the case and non-case populations. We applied 2 different
methods (classification tree analysis and penalized least absolute
shrinkage and selection operator (LASSO) regression) to generate
an algorithm to identify cases from non-cases in men and women
separately. Sensitivity, specificity, positive predictive value (PPV)
and negative predictive value (NPV) were calculated to measure
the algorithm’s accuracy. Sensitivity analyses investigated the influence of SLE prevalence on predictive values.
Results
Both the classification tree method and LASSO regression identified only one variable as the best single discriminator between cases and non-cases: at least one SLE ICD code listed in a specialized
clinic. This resulted in a sensitivity of 0.99 and a PPV of 0.98 in
women. Results in men were similar.
Discussion
The use of an SLE ICD code in a specialized clinic to distinguish
between cases and non-cases performed well. It is possible to identify individuals with SLE among thousands of people in Sweden,
however validation studies are necessary to assess the magnitude
of potential misclassification.
Abstractnummer: 75
75
TWO YEAR FOLLOW-UP ON BIOLOGICS USE IN 13 CENTERS DATA FROM THE INTERNATIONAL REGISTRY FOR BIOLOGICS
IN SLE (IRBIS)
Melinda Mild, Ronald van Vollenhoven, Sören Jacobsen2, Daniel Wallace3, Manel Ramos-Casals4, and for the SLICC group
Karolinska Institutet, ClinTRID, Stockholm, Sverige 2 Köpenhamns
Universitetssjukhus, Köpenmand, Danmark 3 Cedars-Sinai Medical
Center, West Hollywood, United States 4 Hospital Clinic, Barcelona,
Spain
1
Background
Only one biologic agent has been approved for use in SLE, but some
are used off-label. To obtain systematic information regarding this,
the SLICC group initiated the International Registry for Biologics
39
ABSTRACTS
in SLE (IRBIS). Here, data are presented from 13 (of 28) centers for
which two-year-follow-up were available.
Methods
IRBIS investigators provided retrospective data on all patients treated with a biologic at their center in 2010-2011. Demographic-,
disease-specific and treatment-data at biologic initiation and at
yearly follow-ups were collected in standardized CRFs.
Results
In the entire cohort of 455 patients, 84% were treated with rituximab, belimumab 10%, epratuzumab 5% and the remaining with
anti-TNF agents (each <1%). The major organ manifestation leading to biologic treatment was lupus nephritis (LN, 44%); reason
for choosing the biologic was mainly disease-control (73%). At
biologic initiation, mean disease duration (±SD) was 9.5±7.9 years;
mean age was 42.2±12.5. Most patients (91%) were female. Prior to
biologic treatment, most patients (91%) had been treated with ≥1
immunosuppressives. At two-year follow-up (n=120), SLE disease
activity (SLEDAI) and corticosteroid (CS) dose were significantly
lower versus baseline (SLEDAI: 9.4±5.3 to 3.1±2.5; CS: 10.7±13.9 to
4.8±5.9 mg; mean±SD paired analyses, p<0.0001 for both comparisons). At baseline, concomitant CS was used in 91% of patients
compared to 61% at follow-up. SLICC damage-index remained unchanged. There were six deaths, none attributed to the biologic. In
48% of patients there was at least one adverse event reported over
the follow-up period, of which 5% were attributed to the biologic
agent. Serious adverse events included 6 infections, 4 opportunistic infections, 3 posterior reversible encephalopathy syndrome and
4 allergic reactions.
Conclusion
Rituximab was the biologic used most commonly in this international cohort of SLE patients. At two-year-follow-up lupus activity
and concomitant corticosteroid dosage decreased significantly and
corticosteroids were discontinued in 30% of patients.
Abstractnummer: 76
73
OFF-LABEL USE OF RITUXIMAB FOR SLE IN EUROPE: LIMITED
USE MOSTLY IN REFRACTORY PATIENTS
Melinda Mild1, Ronald van Vollenhoven1, Sören Jacobsen2, and
for the SLICC group
Karolinska Institutet, ClinTRID, Stockholm, Sverige 2 Köpenhamns
Universitetssjukhus, Köpenhamn, Danmark
1
Background
Rituximab (RTX) is not approved for use in SLE but has been used
off-label in European countries with efficacy in some patients. We
previously reported, based on the International Registry for Biologics in SLE (IRBIS) and data from investigators, that 0.5-1.3%
of European SLE patients have been treated with RTX. Here, we
compared the characteristics of SLE patients treated with RTX to
those treated with conventional non-biologic immunosuppressives
(ISs).
Methods
Investigators participating in IRBIS, initiated by the SLICC group,
provided data for this study. Data submitted to the IRBIS registry
by 28 centers in 11 European countries were complemented with
additional information from the participating sites. Comparators
were patients started on any conventional IS, not necessarily naïve
for this.
40
Results
One-hundred-and-seventy-five patients were analysed; 103 were
treated off-label with RTX and 72 with IS. Most frequently used
ISs were mycophenolate mofetil (43%) and azathioprine (33%).
For both groups, about 90% were female, 90% caucasians and 85%
non-smokers. Organ manifestations leading to treatment with
RTX or ISs were mainly lupus nephritis (LN, 58% and 53%, respectively). Reason for treatment initiation with RTX was mainly
disease control while steroid sparing was frequently the main reason for ISs. At treatment initiation mean disease duration (±SD)
was 9.1±7.0 for RTX-treated patients and 4.1±6.6 for patients on ISs
(p<0.0001); mean ages were 41.2±12.5 and 36.1±11.3, respectively
(p=0.007). There were significant differences between the groups
for SLEDAI (12.2±7.0 vs. 9.4±7.0; p=0.001) and SLICC damage index
(1.6±3.4 vs. 0.57±1.0, p=0.014).
Conclusion
Both RTX and conventional ISs are mostly used for LN. However,
patients started on RTX were somewhat older, had significantly
longer disease duration, higher disease activity and more damage
compared to patients started on conventional ISs only. These data
support the view that RTX is used for selected patients with later-stage, more severe SLE.
Abstractnummer: 77
75
Application of the 2012 Systemic Lupus International
Collaborating Clinics Classification Criteria On a
Regional Swedish Systemic Lupus Erythematosus Register
Anna Ighe1, Örjan Dahlström2, Th mas Skogh1, Christopher
Sjöwall1
Medicine, Linköping University, Linköping 2 Swedish Institute for
Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping
1
In addition to the 1982 American College of Rheumatology criteria
(ACR-82) for scientific classification of systemic lupus erythematosus (SLE), many clinicians find the ’Fries criteria’ (requiring an
abnormal ANA titer plus ≥two typical organ manifestations) helpful for diagnostic purposes. Last year, the Systemic Lupus International Collaborating Clinics group proposed a new set of validated
classification criteria (SLICC-12), claimed to being more sensitive.
The aim of the present study was to analyze the performance of
SLICC-12 compared to Fries criteria and ACR-82 among well-characterized SLE cases and controls in a regional Swedish register.
The study population consisted of 231 SLE cases (93% Caucasians; 203 women, 28 men; mean age 38.8 years) confirmed by Fries
criteria and/or ACR-82. 53 controls (46 women, 7 men; 40.8 years)
were enrolled on the basis of referral to a rheumatology specialist
based on at least one criterion regarding ’immunologic disorder’
according to ACR-82 and a clinical suspicion of SLE. Sensitivity
and specificity figures for SLE were calculated. All confirmed SLE
cases took part in a prospective follow-up programme at Linköping
University hospital.
Of the confirmed SLE cases, 98% fulfilled Fries criteria, 81% ACR82 and 91% SLICC-12. The combinations of Fries and/or SLICC-12
identified 99%, compared to 93% of all confirmed SLE cases identified by ACR-82 and/or SLICC-12. The sensitivity was high for Fries
(97%) and SLICC-12 (91%), but lower for ACR-82 (79%), whereas
the specificity was superior for ACR-82 (98%) compared to Fries
(83%) and SLICC-12 (75%). We confirm that the ACR-82 criteria
set offers a very high diagnostic specificity, but fail to reveal >20%
ABSTRACTS
of the SLE cases as defined here. The SLICC-12 criteria provide
important additional sensitivity, whereas the specificity was mediocre in this comparison. To increase sensitivity and specificity figures, we advice a combination of the ACR-82 and SLICC-12 criteria
for future studies.
Abstractnummer: 78
73
CUMULATIVE INCIDENCE OF LARGE VESSEL INVOLVEMENT IN
BIOPSY-PROVEN GIANT CELL ARTERITIS
Aladdin Mohammad1,2,3, Carl Turesson2,4
Department of Renal Medicine, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK 2 Reumatologiska kliniken, Skånes Universitetssjukhus 3 Sektionen för Reumatologi, Institutionen
för Kliniska Vetenskaper, Lund, Lunds Universitet 4 Sektionen för
Reumatologi, Institutionen för Kliniska Vetenskaper, Malmö, Lunds
Universitet
1
Abstractnummer: 79
73
Progress Report on the Development of New Classification Criteria for Adult and Juvenile Idiopathic
Inflammatory Myopathies
Anna Tjärnlund, Matteo Bottai, Lisa G Rider, Victoria P Werth,
Clarissa Pilkington, Marianne de Visser, Lars Alfredsson, Anthony Amato, Richard J Barohn, Matthew Liang, Jasvinder A
Jasvinder A Singh, Frederick W Miller, Ingrid E Lundberg1
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden 2 Institute for Environmental Medicine, Karolinska Institutet, Stockholm,
Sweden 3 Environmental Autoimmunity Group, Program of Clinical
Research, National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human
Services, Bethesda, USA 4 Department of Dermatology, Philadelphia
VAMC and Hospital of the University of Pennsylvania, Philadelphia,
USA 5 Department of Rheumatology, Great Ormond Street Hospital
for Children NHS Trust, London, United Kingdom 6 Department of
Neurology, Academic Medical Centre, Amsterdam, Netherlands 7
Department of Neurology, Brigham and Women’s Hospital, Harvard
Medical School, Boston, USA 8 Department of Neurology, University
of Kansas Medical Center, Kansas City, USA 9 Division of Rheumatology, Immunology and Allergy, Brigham and Women´s Hospital,
Boston, USA
1
Background
Inadequate classification criteria for IIM are a fundamental limitation in clinical studies. An international, multidisciplinary collaboration, the International Myositis Classification Criteria Project
(IMCCP), was established to address this problem.
Methods
Candidate variables for classification criteria were assembled from
published criteria and inclusion criteria in controlled myositis
trials. Comparator groups confused with IIM were defined. Clinical and laboratory data from IIM and comparator patients were
collected from 47 rheumatology, dermatology, neurology and pediatrics clinics worldwide from 2008-2011. Crude pair-wise associations among all variables measured and between each variable
and clinician’s diagnosis were assessed. Approaches for derivation
of criteria were: 1. Traditional: case defined by specified number
of items from a set 2. Risk score: patient assigned a probability
risk score by summing score-points associated with the variables
(Probability models 1 and 2) 3. Classification tree: case defined by
a decision tree A random forest algorithm explored the most important variables. Internal validation using bootstrap methods was
performed.
External validation using data from the Euromyositis register and
an UK juvenile myositis register was performed.
Results
Data from 973 IIM patients, representing subgroups of IIM, and
629 comparators were obtained. Comparators include other myopathies and systemic rheumatic diseases. Two probability score
models were developed: Model 1 comprised clinical variables on
muscles, skin, and laboratory measures; Model 2 additionally comprised muscle biopsy variables. Model 1 performed nearly as well
as Model 2 and both models performed as well as and often better
than, the classification tree developed and published criteria. External validation using data on 2363 myositis patients in the Euromyositis register and 332 juvenile myositis cases resulted in >99%
and 100% sensitivity respectively for both probability models.
Conclusion
New classification criteria for IIM with readily clinically assessable measurements and symptoms have been developed. They generally show
superior performance compared with existing criteria.
75
Abstractnummer: 80
Inklusionskroppsmyosit - en eller två sjukdomar?
Ingrid Lundberg1,2, Inger Nennesmo1,2, Snjolaug Arnardottir1,2,
Anna Tjärnlund1,2
1
Karolinska Institutet 2 Karolinska Universitetssjukhuset
Bakgrund
Inklusionskroppsmyosit (IBM) tillhör de inflammatoriska myopatierna. Sjukdomens patogenes är idag omdiskuterad och till stor
del okänd. IBM förekommer både ensam och tillsammans med autoimmuna systemsjukdomar varav Sjögrens syndrom (SS) är vanligast. Sambandet mellan IBM och SS är i dag till stor del outforskat.
Denna studie syftade till att jämföra IBM-patienter utan SS med
IBM-patienter som hade samtidig SS-diagnos för att undersöka
om det finns betydelsefulla skillnader mellan grupperna som skulle kunna leda till en indelning av IBM i olika subgrupper. Material
och metoder: 51 patienter med IBM, varav 10 även hade SS, som
mellan 2003–2013 behandlats på Reumatologiska och Neurologiska klinikerna vid Karolinska Universitetssjukhuset i Solna inkluderades. Grupperna jämfördes utifrån demografiska, kliniska och
laboratoriemässiga variabler. Patientdata inhämtades från journaler och kvalitetsregister.
Resultat
Skillnader som påvisades var att patientgruppen med både IBM
och SS bestod övervägande av kvinnor (p=0,036) med en tidigare
sjukdomsdebut (p=0,098). En mer uttalad muskelsvaghet sågs också i denna grupp, även om den var svårtolkad. Laboratoriemässigt
sågs en förhöjd sänkereaktion (p=0,0015) och vanligare förekomst
av antinukleära antikroppar (p=0,0083).
Slutsatser
De demografiska, laboratoriemässiga och kliniska skillnaderna
utgör preliminära resultat som tyder på att en distinktion mellan
grupperna kan göras. Mer forskning krävs dock för att klinisk til�lämpning ska kunna ske.
41
ABSTRACTS
Abstractnummer: 81
81
CD28NULL T-CELLER DÖDAR AUTOLOGA MUSKELCELLER FRÅN
PATIENTER MED POLYMYOSIT IN VITRO
Jayesh Pandya1, Paulius Venalis1, Lubna Al-Khalili, Mohammad Shahadat Hossain1, Vanessa Stache1, Ingrid Lundberg1,
Vivianne Malmström1, Andreas Fasth1
Enheten för reumatologi, Karolinska univesrsitetssjukhuset Solna,
Karolinska Institutet, Stockholm 2 Sektionen för integrativ fysiologi,
Institutionen för molekylär medicin och kirurgi, K.I, Stockholm
1
Bakgrund
Inflammatory infiltrates of muscles in polymyositis are dominated
by CD4+CD28null and CD8+CD28null T-cells. In contrast to conventional CD28+ T-cells, these cells rapidly release large amounts
of IFN-gamma and TNF and can kill tissue cells by granzyme B and
perforin upon activation.
Syfte
To in a fully autologous system investigate the myotoxic effect of
CD28null T-cells on muscle-cells from polymyositis patients.
Material och metod
Muscle stem cells were extracted from biopsies from 5 patients
with polymyositis, and differentiated into myotubes. T-cell subsets from the same patients were isolated from peripheral blood
by flow-cytometry. Co-cultures of autologous muscle-cells and
unstimulated or pre-activated (anti-CD3-antibodies) T-cells were
performed for 24 hours. Dead myotubes were quantified by calcein
release or by flow-cytometry. Blocking experiments were performed by adding indicated antibodies to the cultures.
Resultat
CD4+CD28null and CD8+CD28null T-cells caused spontaneous
death of 13-60% (n=2 patients) of the muscle-cells. No or low
muscle-cell death was detected in cultures with conventional
CD4+ and CD8+ T-cells. By blocking perforin the myotoxicity was
reduced by 33-62% with CD4+CD28null T-cells and by 42-56% in
cultures with CD8+CD28null T-cells (n=3). TNF or IFN-gamma
did not induce death of muscle-cells in the absence of T-cells, but
did upregulate MHC class I and II on musclecells (n=3-5). Blockade of IFN-gamma and TNF in co-cultures with T-cells reduced the
level of dead muscle-cells by 42-70% (CD4+CD28null) and 10-78%
(CD8+CD28null) (n=3). The reduced myotoxicity is likely attributed to reduced MHC expression, as MHC blockade resulted in a
comparable reduction in myotoxicity, 56-70% (CD4+CD28null)
and 38-95% (CD8+CD28null) (n=5).
Slutsats
The myotoxic effect by CD28null T-cells in polymyositis is mediated by directed perforin-dependent killing and regulated by
IFN-induced MHC expression by muscle-cells. Together this suggests that CD28null T-cells are key effector cells directly contributing to the muscle-cell damage in polymyositis, hence represent
target candidates for future therapies.
Abstractnummer: 82
82
Autophagy May Contribute to Glu- cocorticoid
Resistance in Patients with Myositis by Maintaining T Lymphocytes Homeostasis in the Muscles
Mei Zong1, John Jörholt1, Julia Winter1, Eva Lindroos1, Helena
E Harris1, Ingrid E Lundberg1
42
1
Enheten av reumatologi, Karolinska Universitetssjukhuset
Background
Infiltrating T cells is a typical histopathologic feature in muscles
of myositis patients and they play important roles in disease development. In contrast to macrophages that can be reduced after
glucocorticoid (GC) treatment, T cells often persist. Autophagy
helps cells to survive under cellular stresses. In this context endogenous, cytosolic high mobility group box 1 (HMGB1) is interesting
as HMGB1 can induce autophagy by binding Beclin1 (an upstream
protein initiating autophagy) and thereby contribute to cell survival. Here we investigated whether autophagy initiated by HMGB1-Beclin1 binding contributes to T cell survival and whether this
homeostatic T cells contribute to the GC resistance.
Methods
Muscle biopsies were obtained from poly- and dermatomyositis patients with no or limited clinical response to GC and from
patients with good response. Clinical response was evaluated by
functional index (FI) and serum creatine kinase (CK). Biopsies
were investigated by immunohistochemistry for macrophages
(CD163, CD68), T cells (CD3), HMGB1 and Beclin1. Computer
image analysis was performed. Co-localization of HMGB1, Beclin1
and T cells was done by consecutive section staining and double
immunofluorescence.
Results
HMGB1 and Beclin1 was detected in muscle tissue of patients and
co-localized to the infiltrating T cells. Beclin1 correlated well with
HMGB1, T cells positively and muscle function negatively. In nice
GC responders HMGB1 and Beclin1 expression was decreased after treatment, so was the trend for T cells. Analyses are ongoing on
the non-responders. According to our hypothesis in these patients
T cells will not be reduced as many as in responders after treatment, and HMGB1 and Beclin1 expression will maintain at high
levels.
Conclusion
Autophagy is present in the invading T cells in muscle tissue of
myositis patients. Autophagy initiated by HMGB1- Beclin1 binding
may contribute to T cell survival. These homeostatic T cells could
be a factor contributing to the GC resistance.
Abstractnummer: 83
83
PROFILE OF CIRCULATINING MICRORNAS IN FIBROMYALGIA
AND THEIR RELATION TO SYMPTOM SEVERITY
Jan Bjersing1, Maria Bokarewa1, Kaisa Mannerkorpi2
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg 2
University of Gothenburg Centre for Person-centred Care (GPCC),
Sahlgrenska Academy
1
Abstractnummer: 84
84
DILEMMAS OF PARTICIPATION IN EVERYDAY LIFE IN EARLY
RHEUMATOID ARTHRITIS (RA), A QUALITATIVE INTERVIEW
STUDY (The Swedish TIRA study).
Annette Sverker1, Gunnel Östlund, Mikael Thyberg, Eva Waltersson1, Mathilda Björk, Ingrid Thyberg
1
Rehabgruppen NSC Universitetssjukhuset i Linköping, Landsting-
ABSTRACTS
et i Östergötland 2 Avdelning för socialt arbete, Akademin för hälsa,
vård och välfärd, Mälardalens högskola. 3 Institutionen för klinisk
och experimentell medicin, Linköpings universitet, Länskliniken för
reumatologi, Landstinget i Östergötland. 4 Rehabiliteringsmedicin,
Institutionen för Medicin och Hälsa, Linköpings Universitet, 5 Avdelningen för socialt arbete; Institutionen för samhälls och välfärdsstudier, Linköpings Universitet
Background
An important perspective in research is the patients´ own experiences of how it is to live with RA, in terms of dilemmas and consequences in everyday life. Although there have been improvements in
the outcomes due to the pharmacological treatment, RA still has an
impact on functioning. The aim was to explore dilemmas of participation experienced in everyday life in early RA.
We interviewed 48 patients, age 20 – 63, with early RA about participation dilemmas in everyday life, with Critical Incident Technique. Transcribed interviews were condensed into meaningful
units describing situations. In next step, these descriptions were
linked to ICF activity/participation codes according to ICF linking
rules. Dilemmas related to ICF activity/participation according to
domestic life, interpersonal interactions/relationships, community, social and civic lives are reported here.
Results
Regarding domestic life dilemmas were linked to acquisition of
goods and services, preparing meals, doing housework, caring for
household objects and assisting others. Regarding interpersonal
interactions and relationships the dilemmas were linked to basic
interpersonal interactions, complex interpersonal interactions,
relating with strangers, informal social relationships, family relationships and intimate relationships. About community, social and
civic life dilemmas were linked to community life, recreation and
leisure, and religion and spirituality. The described ICF-linked dilemmas were also linked to each other. For instance dilemmas related to community life are combined with dilemmas within mobility
such as lifting and carrying objects and moving objects with lower
extremities when being active in an association. Other combined
dilemmas concern interpersonal interactions and relationships
such as refraining from attending a wedding party due to fear of
shaking hands with people or not engaging in association activities
when not having the energy to engage in other people.
Conclusion
The results illustrate patterns of participation restrictions in early
RA. Awareness about described patterns is relevant to comprehensive multidisciplinary assesements.
Abstractnummer: 85
85
Emotions related to participation restrictions
experienced by patients with early rheumatoid arthritis: A qualitative interview study (The Swedish
TIRA study)
Gunnel Östlund1, Mathilda Björk2,3,4, Ingrid Thyberg2,4, Mikael
Thyberg4, Eva Valtersson2, Birgitta Stenström5, Annette Sverker2
1
Division of Social Work, School of Health, Care and Social Welfare, Mälardalen University 2 County Council of Östergötland 3 Jönköping University 4 Linköping University 5 The Swedish Rheumatism Association
Background
Psychological distress is a well-known complication in rheumatoid
arthritis (RA). It is usually studied by questionnaires with predefined items related to mental functions, and the knowledge regarding the full spectrum of emotions and their relations to practical
participation restrictions is still scarce.
Objectives
The aim was to explore emotions related to participation restrictions.
Method
This study is part of the Swedish TIRA-project. 48 patients with
early RA, age 20 – 63, were interviewed about participation restrictions with Critical Incident Technique. Transcribed interviews
were synthesized into dilemmas and linked to ICF activity/participation codes. The emotions described by the patients have been
condensed and categorized.
Results
Sadness, fear, anger, and shame were expressed in relation to RA
participation restrictions. Sadness was described when trying to
perform daily activities such as getting up in the mornings, getting
dressed, or at work when not being able to perform duties.
Sadness was also experienced in relation to not being able to continue leisure activities or in caring for children. Examples of fear
descriptions were found in relation to the deteriorating health and
fumble fear made the individual withdraw from activities when
mistrusting the body. Anger was described in relation to domestic
and employed work, but also in social relations when the individual felt hindered to continue valued activities. Shame or embarrassments were described when participation restrictions became
visible in public.
Conclusions
Sadness, anger, fear and shame are closely related to practical participation restrictions and may be addressed by corresponding multiprofessional interventions that facilitate participation.
86
Abstractnummer: 86
The GOT-NET Study – A randomized study evaluating the efficacy of nurse-led clinic compared to
patients receiving regular care, a study protocol
description.
Ulrika Bergsten, Lennart Jacobsson1
Göteborgs Universitet, Avdelningen för Reumatologi och inflammationsforskning
1
Purpose
To compare a nurse-led clinic including person-centered care
and tight control with “care as usual” in patients with rheumatoid
arthritis (RA) and moderate/ high disease activity.
Project description
Study population: Patients with RA, 18-80 years old, with moderate/ high Disease Activity Score of 28 joints (DAS28 > 3.8) and
disease duration > 2 years in a 6-month randomized controlled
study with a 6 month open follow-up. Intervention group (N=60):
Nurse-led visits every 6th week, with structured person-centered care and evaluation of disease activity. If disease remission
is not reached, pharmacological treatment including both shortterm (intra-articular and oral steroids) and long-term alterations
(DMARDs and biologics) is modified according to a predefined algorithm. The control group (N=60) is treated according to “care as
usual” with visits to physician every 6th month.
43
ABSTRACTS
Outcome measures
Primary outcome measure is change in Diseases Activity Score
(DAS) at week 26. Secondary outcomes are; compare the proportion of patients with low diseases activity and proportions of remission and EULAR response, quality of life, self-efficacy, disability, emotional well-being, pain, fatigue, sleep and satisfaction at
week 26 and 50. The study starts in January 2014 and will be ongoing for at least 2 years.
Expected outcomes
Based on “regular care” data from 2012, only 30 % of out-patient
care of RA patients with the above inclusion criteria will reach the
low disease activity (DAS28 < 3,2) at follow-up. The present study aim to compare this “regular care” with a model based on nurse-led clinics with person-centered care and tight disease control.
If effective, this model could easily be implemented in the health
care system.
Abstractnummer: 87
87
SAMBAND MELLAN FATIGUE, NEDSTÄMDHET OCH LIVSKVALITET VID PRIMÄRT SJÖGRENS SYNDROM
Rezvan Kiani1, Lilian Vasaitis2, Gunnel Nordmark2
Reumatologsektionen, Institutionen för folkhälso- och vårdvetenskap, Uppsala Universitet 2 Reumatologsektionen, Institutionen för
medicinska vetenskaper, Uppsala Universitet
1
Bakgrund
Vid primärt Sjögrens syndrom (pSS) är en förlamande trötthet, fatigue, ofta ett dominerande symptom. Orsakerna är inte klarlagda
men behandlingsbara tillstånd såsom nedstämdhet kan bidra. Syftet med denna studie var att identifiera förekomsten av fatigue hos
patienter med pSS, studera sambandet med nedstämdhet, ångest
och livskvalitet samt med autoantikroppar, extraglandulära manifestationer, inflammationsparametrar och blodvärde.
Material och metod
Åttiotvå patienter med pSS inbjöds att delta i studien varav 62
(75,6 %) tackade ja. Fyra instrument besvarades; VAS fatigue, Eular Sjögren’s Syndrome Patient Reported index (ESSPRI), Hospital
Anxiety and Depression Scale (HADS) och Short Form-36 (SF-36).
Förekomst av SSA/SSB-antikroppar och extraglandulära manifestationer hämtades ur journalerna. SR, CRP och Hb togs vid besöket.
Resultat
Totalt 45/62 patienter (72,6 %) skattade hög VAS fatigue (≥50 mm)
vilket korrelerade med ESSPRI fatigue (r2=0,8). Det var ingen
skillnad i autoantikroppar eller extraglandulära manifestationer
mellan patienter med hög (≥50 mm) respektive låg (<50 mm) fatigue. Totalt 19 % av patienterna erhöll >8/21 poäng för depression
och 26 % fick >8/21 poäng för ångest, indikerande sjuklighet. VAS
fatigue korrelerade starkt med poängen för nedstämdhet (HADS
D) och ångest (HADS-A), (r2=0,24-0,26, p<0,0001). Patienterna
skattade sin livskvalitet i SF 36 som låg jämfört med publicerade
åldersmatchade friska kontroller1. VAS fatigue korrelerade med
samtliga domäner i SF-36, (r2=0,1-0,4, p<0,01). Det fanns inte något
samband mellan fatigue och SR, CRP eller Hb.
Slutsats
Hög fatigue förekommer hos cirka tre fjärdedelar av patienterna
med pSS vid vår mottagning och korrelerar till nedstämdhet, ångest och nedsatt livskvalitet. Det finns inget samband mellan fatigue
och autoantikroppar, extraglandulära manifestationer, SR, CRP
eller Hb. Identifiering och behandling av nedstämdhet och ångest
44
kan möjligen minska tröttheten hos en grupp av patienter med pSS.
Referens
(1) Segal B et al. Health and quality of life outcomes, 2009; 7: 46.
Abstractnummer: 88
88
Valued life activities: Swedish version (VLA-swe) with
cultural adaption, ICF linkage, psychometric testing
Mathilda Björk1, Mikael Thyberg2, Eva Valtersson3, Patricia Katz4
Rehabenheten, HMC, Universitetssjukhuset i Linköping 2 Avdelningen för rehabiliteringsmedicin, Hälsouniversitetet i Linköping
3
NSC, Universitetssjukhuset i Linköping 4 Department of Rheumatology, University of California, San Fransisco
1
Background
Disability is an important outcome in rheumatoid arthritis (RA).
The Valued Life Activity scale (VLA) comprises a wide range of life
activities deemed to be important by the individual.
Objectives
Translation, cultural adaptation including linkage to the International Classification of Functioning, Disability and Health (ICF) and
psychometric testing of the VLA scale in Swedish patients with RA.
Methods
The VLA was translated and culturally adapted to a Swedish version, the VLA- swe. Both the VLA and VLA-swe were linked to the
ICF according to linking rules. 737 RA patients(73% women)aged
18 - 80 (mean age 62 years) were recruited from the Swedish Rheumatology Quality Registry (SRQ). The average disease duration
was 16 years. Data for disease activity (DAS28), activity limitations
(HAQ) and life satisfaction (LiSat11) were registered and patients
completed the VLA-swe. Internal consistency was assessed with
Cronbach’s alpha and item statistics. To establish construct validity
VLA-swe was correlated to DAS28, HAQ and LiSat11. Results: The
conceptual similarity between the VLA-swe and the original VLA
was high when linked to the ICF. Each of the 9 ICF activity/participation domains was represented in one or more items. The internal consistency was excellent for the VLA- swe (0.97) and alpha
coefficients did not improve after omitting any of the 33 items. The
correlations between the single items and the total VLA-swe score
varied between r=0.57 and r=0.84. Scores of the VLA-swe correlated strongly with the HAQ (r=0.87), moderately with the LiSat11
(r=-0.61) and weakly with the DAS28 (r=0.38), as expected.
Conclusions
The VLA-swe is culturally adapted and validated, and addresses a
broad range of ICF activity/participation domains. Since both the
patients ́ preferences and ICF concepts of disability are taken into
account, it is a useful complement to traditional measures, such as
the HAQ, which measure activity limitations only.
Abstractnummer: 89
89
THE EXERCISE BENEFITS/BARRIERS SCALE - TEST-RETEST RELIABILITET OCH SAMBAND MED FYSISK AKTIVITETSNIVÅ OCH
UPPLEVD HÄLSA
Maria Svedling1, Nina Brodin2
Hälsopoolen Rehabklinik, Södermalm, Stockholm 2 Karolinska
Institutet Institutionen för Neurobiologi, Vårdvetenskap och samhälle, Sektionen för Sjukgymnastik
1
ABSTRACTS
Bakgrund
Ankyloserande spondylit (AS) leder till stora begränsningar i individens funktion och aktivitetsnivå. Fysisk aktivitet är en av hörnstenarna i behandlingen av individer med AS. Trots det är knappt
hälften av individer med AS regelbundet fysiskt aktiva. Exercise
benefits/barrier scale (EBBS) är ett frågeformulär som används för
att bedöma fördelar och hinder med fysisk aktivitet.
Det har tidigare inte funnits tillgängligt på svenska och inte använts på individer med AS i Sverige.
Syfte
Att beskriva test-retest reliabilitet hos den svenska versionen av
EBBS samt att studera samband mellan EBBS och fysisk aktivitetsnivå respektive upplevd hälsa hos individer med AS.
Material och metod
Trettiotvå individer med AS deltog i studien. Test-retest reliabilitet
av EBBS undersöktes med en veckas mellanrum. För att beskriva
samband med fysisk aktivitetsnivå och upplevd hälsa användes
The International Physical Activity Questionnaire (IPAQ) och delskalor i The short form-36 (SF-36).
Resultat
Test-retest reliabilitet var god för de tre kategorierna EBBS totalsumma (ICC 0.818, 95% CI 0.659 – 0.907), EBBS benefits (ICC
0.806, 95% CI 0.639-0.900) samt EBBS barriers (ICC 0.820, 95%
CI 0.662-0.908). De 14 frågorna om barriers visade måttlig till god
överensstämmelse enligt viktad Kappa (Kw) (Kw 0.526-0.860)
utan systematiska skillnader (p > 0.05). Av de 29 frågorna om benefits visade 11 svag överensstämmelse (Kw 0.200-0.389) och övriga
18 måttlig till god överensstämmelse (Kw 0.422-0.813) utan systematiska skillnader (p > 0.05). Spearman korrelationer mellan EBBS
och fysisk aktivitetsnivå eller upplevd hälsa var alla mycket låga till
låga (rs 0.05-0.34).
Slutsats
EBBS är ett reliabelt instrument hos individer med AS. Vissa av de inkluderade frågorna visade dock låg överensstämmelse vid upprepat
test. Detta sammantaget med att endast mycket låga samband mellan
EBBS och fysisk aktivitetsnivå respektive upplevd hälsa sågs kan indikera att instrumentet har bristande validitet för att bedöma hinder
och fördelar med fysisk aktivitet hos individer med AS.
Abstractnummer: 90
90
LOW LEVELS OF PAIN IMPACT ON VALUED LIFE ACTIVITIES IN
WOMEN AND MEN WITH RHEUMATOID ARTHRITIS
Inger Ahlstrand1, Mathilda Björk1,2,3, Ingrid Thyberg2,3, Torbjörn
Falkmer1,3,4,5
Hälsohögskolan, Högskolan i Jönköping 2 Reumatologkliniken,
Universitetssjukhuset i Linköping 3 Linköpings universitet 4 School
of Occupational Therapy & Social Work, CHIRI, Curtin University,
Perth, WA 5 School of Occupational Therapy, La Trobe University,
Melbourne, Australia
1
Background
Disability in Rheumatoid Arthritis (RA) is more pronounced in
women than in men and pain is strongly related to activity limitation and participation. The Valued life activity scale (VLA) is a
questionnaire in which patient’s first report if the activities are
valued or not to perform and secondly difficulties to perform these activities. To measure disability with VLA includes the patient’s
perspective in a unique way compared to traditional disability measurements (e.g., HAQ).
Objective
To examine difficulties to perform valued life activities and how
these difficulties were related to pain in women and men with RA.
Methods
In total, 737 persons with RA (73% women) from three rheumatology’ units in Sweden responded to a questionnaire measuring
performance of 33 valued life activities and pain. The relationship
between performance of valued life activities and pain were analysed based on gender and pain intensity. Multiple linear regression
analyses were carried out with the total VLA score as dependent
variable.
Results
Women reported more pain and difficulties in performing valued
life activities than men. Across genders, 85% reported at least one
valued life activity affected by RA. Significantly more women than
men encountered difficulties in performing some activities such
as cooking, gardening and meeting new people. Women reported
higher pain intensity (35 mm VAS) than men (31 mm VAS). Almost
all 33 difficulty ratings for valued life activities were higher among
persons with high pain (VAS>40 mm) than persons with lower
pain. Difficulty ratings for valued life activities correlated positively with pain in persons with lower pain, but not among those with
high pain.
Conclusions
The results highlight the importance of addressing pain especially
among women with RA as they reported pain to impact on their
valued life activities. Interestingly, this was evident also in women
with lower levels of pain.
Abstractnummer: 91
91
COST-EFFECTIVENESS OF A ONE-YEAR COACHING PROGRAM
FOR HEALTHY PHYSICAL ACTIVITY IN EARLY RHEUMATOID
ARTHRITIS
Nina Brodin1,2, Malin Lohela-Karlsson3, Emma Swärdh1, Christina H Opava1,4
Karolinska Institutet, Institutionen för Neurobiologi, Vårdvetenskap och Samhälle, Sektionen för sjukgymnastik 2 Danderyds Sjukhus,
Oprtopedkliniken, Paramedicinska sektionen 3 Karolinska Institutet,
Institutet för miljömedicin, Institutionen för Interventions- och implementeringsforskning 4 Karolinska Universitetssjukhuset, Reumatologiska kliniken
1
Background
Economic evaluations of interventions, as a complement to the effect evaluation, intend to inform decision makers about whether
the intervention provides good value for the money. Since resources in healthcare are scarce, there is an increased demand from decision makers for economic evaluations. Economic evaluations of
non-pharmacologic care in RA are still not as commonly presented
as evaluations of the costs related to medications.
Purpose
To describe cost-effectiveness of the Physical Activity in Rheumatoid Arthritis study intervention overall and for different subgroups. At the CARE VI meeting, the importance of such evaluations was acknowledged.
Method
Costs were collected and estimated retrospectively. Cost-effectiveness was calculated based on the intervention cost per patient
45
ABSTRACTS
with respect to change in health status (EuroQol global visual analog scale, EQ-VAS, and EuroQol, EQ-5D) and activity limitation
(Health assessment questionnaire, HAQ) using cost-effectiveness-,
and cost-minimization analyses.
Results
Total cost of the one-year intervention program was estimated to
€67317 or €716 per participant. Estimated difference in total societal cost between the intervention (IG) and control (CG) was
€580 per participant. Incremental cost-effectiveness ratio (ICER)
for one point (1/100) of improvement in EQ-VAS was estimated
to €116. By offering the intervention to more affected participants
(MO) in the IG compared to less affected participants (LE), 15.5
extra points of improvement in EQ-VAS and 0.13 points of improvement on HAQ were gained at the same cost. ‘Ordinary physiotherapy’ was most cost-effective with regard to EQ-5D.
re ansåg att FA är ett viktigt hälsomål för patienter och rekommenderade regelbundet FA till sina patienter. 70 %, 89 % respektive
96 % ansåg att folkhälsorekommendationer avseende måttligt ansträngande FA var lämpliga för patienter med RA och de användes
av 36 %, 90 % respektive 91 % i Holland, Italien och Sverige. I medeltal skattade deltagare sin kompetens för att främja FA som 6.3, 7.1
och 5.6 av 10, och 69 %, 89 % respektive 71 % uttryckte ett behov av
ytterligare utbildning inom området.
Konklusion
FA enligt folkhälsorekommendationer för personer med RA anses
lämpligt, men rekommenderas hälften så ofta i Holland som i Italien
och Sverige. Den upplevda kompetensen för att främja FA var lägst i
Sverige och högst i Italien avseende samtliga frågor.
Abstractnummer: 93
93
Conclusions
The intervention resulted in improved effect in health status for
the IG with a cost of €116 per extra point in VAS. The intervention
was cost-effective if targeted towards a subgroup of more affected
patients when evaluating the effect using VAS and HAQ.
Reliabilitet och validitet hos modifierad Fear- Avoidance Beliefs Questionnaire i en poulation med reumatoid artrit
Abstractnummer: 92
1
92
ATT FRÄMJA FYSISK AKTIVITET - EN JÄMFÖRANDE STUDIE
MELLAN HOLLAND, ITALIEN OCH SVERIGE OM ATTITYDER
OCH KUNSKAP HOS VÅRDPERSONAL
Nina Brodin1, Emalie Hurkmans, Luigi Di Matteo, Tiziana
Nava, Thea Vliet Vlieland, Christina H Opava1
Karolinska Institutet, Institutionen för Neurobiologi, Vårdvetenskap
och Samhälle, Sektionen för sjukgymnastik 2 Danderyds sjukhus, Ortopedkliniken, Paramedicinska sektionen 3 University of Applied Sciences, Vienna, Austria 4 Local Hospital, ASL, Pescara, Italy 5 University
of Milan, Italy 6 Leiden University Medicla Center, the Netherlands 7
Karolinska Universitetssjukhuset, Reumatologiska kliniken
1
Bakgrund
Personer med reumatoid artrit (RA) är i många fall fysiskt inaktiva, trots att bevis finns för många hälsovinster av en fysiskt aktiv
livsstil. Effektiva metoder för att främja fysisk aktivitet (FA) har
utvecklats, men kunskap saknas kring i vilken utsträckning vårdpersonal inom reumatologi (reumatologer, sjuksköterskor, sjukgymnaster) använder sig av dessa.
Syfte
Att beskriva och jämföra attityder hos vårdpersonal i Holland, Italien och Sverige avseende FA, i vilken utsträckning FA rekommenderas, upplevd kompetens avseende främjande av FA samt eventuellt utbildningsbehov inom området.
Metod
Frågeformulär distribuerades till 700 Holländska, 1402 Italienska
och 837 Svenska reumatologer, sjuksköterskor och sjukgymnaster
inom reumatologi. Frågeformuläret innehöll 23 frågor om främjande av FA och utvecklades för den ursprungliga holländska studien
och översattes till italienska och svenska enligt gängse standardiserade procedur.
Resultat
Svarsfrekvensen var 53 % i Holland, 25 % I Italien och 29 % I Sverige. Medelålder var 45.8, 41.3 och 52.6 år i respektive land och klinisk erfarenhet inom reumatologi var 13.3, 16.6 respektive 24.7 år.
98 % av holländska, 96 % av italienska och 99 % av svenska deltaga46
Anna Dahlgren, MSc, Ingrid Demmelmaier, PhD Abstract
Karolinska Institutet, Institutionen för neurobiologi, vårdvetenskap
och samhälle, sektionen för sjukgymnastik
Bakgrund
Syftet var att undersöka reliabilitet och validitet hos mätinstrumentet modifierad Fear- Avoidance Beliefs Questionnaire (mFABQ) i en population med reumatoid artrit (RA).
Material och metod
Studien är en psykometrisk studie med upprepad mätning för bestämning av test-retestreliabilitet och tvärsnittsanalyser för bestämning av inre överensstämmelse och begreppsvaliditet. Datainsamlingen gjordes inom en större studie (PARA 2010) för individer
med RA. Test-retestreliabilitet analyserades med viktad Kappa
(n=179). Inre överensstämmelse analyserades med item-to-total
correlation (n=216) och begreppsvaliditet med korrelationsanalyser (n=216). mFABQ ingick i ett formulär som fylldes i av deltagarna vid två tillfällen med 4-6 månaders mellanrum före interventionen i PARA 2010.
Resultat
Enligt beräkning av kappavärden var test-retestreliabiliteten låg
till måttlig (0.28-0.42) i varje enskilt item, liksom korrelationen
för totalsumman (rs= 0.53, p<0.001). Den inre överensstämmelsen
mätt med item-to-total correlation var låg till måttlig (0.22-0.63,
p<0.001). Begreppsvaliditeten stärktes i fem av de sex i förväg uppställda hypoteserna vad gällde korrelationer med förväntningar
på fysisk aktivitet (rs= -0.17, p<0.05; rs= -0.02, p<0.01), smärta (rs=
0.36, p<0.001), ålder och kön (inga signifikanta korrelationer).
Slutsats
Reliabiliteten och validiteten behöver undersökas vidare för att säkra
den kliniska användbarheten av mFABQ för individer med RA. Resultatet för test-retestreliabiliteten i studien förklaras sannolikt till
stor del av att tiden mellan de två mättillfällena var för lång. Fortsatt psykometrisk testning bör göras i studier med detta som primärt
syfte, och validera instrumentet gentemot t.ex. aktivitetsbegränsning
och nedstämdhet, som ingår i fear-avoidancemodellen.
Abstractnummer: 94
94
HAND PAINS IN WOMEN AND MEN IN EARLY RA, A ONE YEAR
FOLLOW UP AFTER DIAGNOSIS IN THE TIRA-2 COHORT
ABSTRACTS
Ingrid Thyberg1, Örjan Dahlström2, Mathilda Björk3,4,5, Birgitta Stenström1, Jo Adams6
Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Department
of Rheumatology in Östergötland, County Council of Östergötland,
Linköping, Sweden 2 Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Sweden 3 Rehabilitation section, County Council of Östergötland,
Linköping, Sweden 4 Department of Rehabilitation, School of Health
Sciences, Jönköping University, Sweden 5 Division of Community
Medicine, Rehabilitation medicine, Faculty of Health Sciences, Linköping University 6 Centre for Innovation and Leadership, Faculty of
Health Sciences University of Southampton
1
Objectives
To analyze general pain intensity, hand pain at rest and hand pain
during activity in women and men in early RA.
Methods
Out of the 454 patients that were recruited into the Swedish early
RA project “TIRA” the 373 patients (67% women) that remained at
12 months follow up are reported here. Disease activity (DAS-28)
and pain (VAS) was registered at inclusion and at 3 (M3), 6 (M6),
and 12 (M12) months. General pain, hand pain during rest, hand
pain during test of grip force by Grippit , prescribed diseasemodifying anti-inflammatory drugs (DMARDs) and hand dominance
was registered.
Results
Women had somewhat higher DAS and somewhat more prescribed DMARD:s than men. The difference was significant regarding
DMARD:s at M3. All pain types were significant higher at inclusion than at the follow-ups and women reported significant higher
pain than men at the follow-ups but not at inclusion. The pain types were significantly different, general pain was highest and hand
pain at rest was lowest. A significant interaction between pain-type
and follow-up showed that the three pain types differed at each
follow-up but for general pain and hand pain during activity at M3.
There were no significant differences in hand pain related to hand
dominance or between right and left hand.
ded. At admission and discharge the patients were evaluated with
measures on functioning (HAQ), self-efficacy (ASES), psychological health (HSCL-25), pain and fatigue and on health related quality of life (HRQoL) as captured by the EQ-5D and the SF-36. The
patients set individual goals for their rehabilitation. At discharge
the patients reported if the goals were achieved completely, partially or not at all.
Results
108/146 patients reported level of goalachievement, and were
included in further analyses, 76% were females and 55% had RA.
At baseline median age was 54 years (IQR 17), median HAQ 0.88
(IQR 0.88), median HRQoL as captured by EQ-5D 0.62 (IQR 0.57),
median psychological wellbeing according to HSCL-25 1.62 (IQR
0.68), median fatigue 6.0 (IQR 4.0) and pain 5.0 (IQR 3.0).
The rehabilitation program lasted for median 18 days (IQR 2).
58/108 patients (54%) rated their goal to be completely achieved,
40 patients (37%) reported partial goal achievement while 10 (9%)
patients had not achieved their goal. Positive reporting of compliance during the rehabilitation was obtained from 100 (93%) of the
patients.
Change after intervention and compliance did not affect reports of
goal achievement after rehabilitation. Females reported goal
achievement more often than men did (p=0.019). Those not
achieving their goals reported less psychological wellbeing (HSCL25, p=0.011) at admission together with reports of worse pain (SF36bp, p=0.011).
Conclusion
54% of the included patients reported complete goal achievement
after arthritis team rehabilitation. Neither change after intervention nor compliance affected patients’ reports of goal achievement.
Female patients were more prone to achieve their goals. Patients
experiencing less psychological wellbeing or more pain at baseline
were less prone to report goal achievement.
Conclusions
Overall women reported higher pain than men at the follow-ups. Hand
pain in activity was higher than pain during rest, strongly indicating
that hand pain is closely related to hand related activities.
Abstractnummer: 95
95
WHO WILL ACHIEVE INDIVIDUALLY SET GOALS AFTER ARTHRITIS TEAM REHABILITATION?
Sofia Hagel1, Elisabet Lindqvist1, Ann Bremander2,3
Institutionen för Kliniska Vetenskaper Lund, avdelningen för
Reumatologi. Lunds Universitet och Skånes Universitetssjukvård 2
FoU-centrum Spenshult, Halmstad, 3 Institutionen för Kliniska Vetenskaper Lund, avdelningen för Reumatologi, Lunds Universitet
1
Background/Purpose
To study goal achievement among patients with chronic inflammatory arthritis after arthritis team rehabilitation.
Materials and methods
146 consecutive patients with rheumatoid arthritis (RA) and spondyloarthritis, completing team rehabilitation program, were inclu-
47
ReumaKalender
2014
Reumadagarna
1 april
1–4 april, Örebro
www.reumadagarna2014.se
1 maj
The Extracellular matrix
The legacy of Dick Heinegård. Center for
Biochemistry, University of Cologne,
Germany. May 1-3, 2014
12 maj
Kroniska artritsjukdomar – diagnostik,
patogenes och behandling
SK-kurs, Stockholm 12-16/5
19 maj
Nationella ST-dagar i reumatologi
19–20 maj, Umeå
Tema: Infektioner som orsak till och
komplikation vid reumatisk sjukdom.
12 sept
Farmakoterapikurs
SK-kurs, 8-12 september, Lund
21 sept
Scandinavian Congress of Rheumatology
21-23 september, Stockholm
16 okt
Cutting Edge Rheumatology Symposium
16 oktober, Lund
14 nov
ACR/ARHP Annual Meeting
14-19 november, Boston
24 nov
SK-Kurs Reumatologisk immunologi
24-28 november, Göteborg
11 juni
EULAR Congress 2014
11–14 juni, Paris
www.eular.org
Information/program/inbjudan återfinnes i Reumakalendern på www.svenskreumatologi.se
Pottholtz funderingar enligt Tomas Weitoft
48

REUMADAGARNA 2014 - Svensk Reumatologisk Förening

Transcription

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