Arthritis Research UK

Transcription

arthritis
the magazine
reporting research,
treatment and
education
SPRING 2009
No 144
Anti -TNF
– what
comes
next?
New report on
complementary
medicines – do
they work?
Osteoarthritis – a radical new approach
The search for the rheumatoid arthritis ‘Holy Grail’
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NUTRITION FOR A HEALTHY LIFESPAN
arthritis
CONTENTS
W
elcome to the spring edition of Arthritis
Today. The advent of arc’s anti-TNF
therapy has transformed the treatment
of rheumatoid arthritis but it has also spawned a
host of other exciting new drugs, which are now
in the pipeline. On page 8, leading researcher and
clinician Paul Emery talks about how inducing
disease remission is a very real possibility. David
Felson from Boston University is an internationally
renowned authority on osteoarthritis, and over the
next five years he will be splitting his time between
the US and the UK, where he is to lead a series of
major arc-funded clinical trials. Read an interview
with Professor Felson on p15. Complementary
medicines for arthritis can cure just about
everything according to the popular press but what
does the actual evidence say? arc has produced its
own authoritative report on what works and what
doesn’t. Find out more on page 12. Research into
inflammatory arthritis at King’s College London
has been boosted by the appointment of two new
arc professors for the price of one, see page 28.
And on page 18, you can find out how a series of
practical clinical trials at our new national primary
care centre at Keele University will have an equally
practical impact on patients.
Jane Tadman,
Editor, Arthritis Today
arthritis
The Arthritis Research Campaign (arc) is a medical
research charity entirely supported by voluntary
contributions and legacies.
For further information about the charity and its work
contact:
Arthritis Research Campaign, St Mary’s Gate,
Chesterfield, Derbyshire, S41 7TD.
Tel: 01246 558033 Fax: 01246 558007
Email: [email protected] Website: www.arc.org.uk
Arthritis Today is available through local branch
subscription or for an annual donation of £15.
Editor: Jane Tadman
Designer: Jonathan Ogilvie
Correspondence to the editor should be sent to the
address above or to [email protected]
Advertising sales: Claire Barber, Redactive Media Group,
17 Britton Street, London, EC1M 5TP.
Printed by PPS Charisma Ltd., Building 2, Orgreave Drive,
Sheffield, South Yorkshire, S13 9NR.
Arthritis Today|Spring 2009|www.arc.org.uk
4
4
News
New national primary care centre
opens; stem cell research to treat back
pain; NICE guidance on rheumatoid
arthritis
8
What’s next after anti-TNF?
Paul Emery on new drugs for
rheumatoid arthritis
12 Complementary medicines
– through the minefield
Our new 80-page report on what
works and what doesn’t – according to
scientific evidence
12
15 A new way of looking at
osteoarthritis
David Felson on his radical new
research programme
17 Research grants awarded
Who’s been awarded what
18 Knee pain on trial
How successive clinical trials are
developing better treatments
20 Back to Basics
Postgraduate research at the
University of Newcastle
23 The Hints Box
26
Readers share their tips
24 Spotlight on Science
Professor Vic Duance and Dr Bahaa
Seedhom explain what they do with
your money
26 Questions and Answers
Dr Philip Helliwell answers readers’
queries
28 Focus on King’s College
London
arc’s two new Professors and their
plans
32 Fundraising
A round-up of head office and
community fundraising news
28
None of the products or services advertised in Arthritis Today are in
any way endorsed by the Arthritis Research Campaign.
Front cover: arc Professor of Rheumatology at the University
of Leeds, Paul Emery. See page 8.
Registered Charity No.207711
4
News
arc professor receives
recognition for research
An arc professor has been
recognised as one of the
leading medical researchers in
Scotland.
Lord Darzi (right) pictured with the Vice Chancellor of Keele University Professor
Dame Janet Finch and chairman of arc trustees Charles Maisey
Stuart Ralston, who is the arc
Professor of Rheumatology at
the University of Edinburgh,
has won the 2008 Margaret
McLellan award for his
research into the causes and
treatment of bone diseases.
The first of arc’s national centres of research excellence was
opened by government health minister Lord Darzi in December.
The award is presented every
two years by the medical
charity Tenovus Scotland in
recognition of outstanding
contributions to medical
science. This year, the field of
bone health was selected as
the topic for the £2,000 prize.
With funding of £2.5m over five years, the centre is dedicated to
preventing common musculoskeletal conditions from starting,
getting worse or limiting people in their daily lives, and to support
the provision of effective treatment and help for these conditions in
primary care and the community.
Professor Ralston, who is lead
clinician for the osteoporosis
service in NHS Lothian, has
been conducting research into
various bone diseases over
First new national centre of
excellence opened
Its aim is to provide evidence from scientific research on how best
to meet these challenges. The centre’s programme of research is a
joint venture between the university and local NHS organisations.
Centre director Professor Peter Croft said: “Our new centre will give
a strong message that primary care is vitally important and that a
major national charity values research in that setting. “Lord Darzi’s report this year on the National Health Service
highlighted the need for the NHS to value results that are important
to patients – less pain, improved sense of wellbeing and being
satisfied with the care they have received. These are precisely
the outcomes which arc wants the new centre to study and our
research programme is geared to finding out how to achieve these
for patients with conditions such as back pain and osteoarthritis.”
arc chief executive Fergus Logan added: “We have established
the new centre at Keele because primary carers such as GPs,
physiotherapists, nurses and podiatrists see by far the largest
number of people who have
arthritis and musculoskeletal
conditions, and under the new
Department of Health, policies
will be required to see and treat
even more. Yet as things stand
less than one third of people
with osteoarthritis are receiving
appropriate treatment.
“Clearly there is a major task
to be performed not only to
develop clinically proven best
practice but also to encourage
its use. We expect our new
centre at Keele to play a huge
part in fulfilling this aim.”
Professor Peter Croft
the past 25 years including
osteoporosis, Paget’s disease
of bone and bone disease
in patients with cancer. His
research has helped to unravel
the genetic contribution
to bone disease and he is
currently leading a major
clinical arc-funded trial to try
and prevent the development
of Paget’s disease, and a
major study into the effects of
cannabis on bone health.
New trustees join arc
arc has recruited four new
members to its board of trustees
with vastly differing areas of
expertise. The appointments
come as the charity moves
forward with its strategy of
focusing on and investing in new
treatments and techniques which
will have an immediate impact
on patients, as well as developing
innovative research schemes.
Welcoming the new members
to the board, chief executive
Fergus Logan said: “To support
and guide our expansionist
programme requires governance
of the highest quality, and arc
is delighted to announce the
recruitment of four new trustees
whose background and expertise
provides just that.”
Sir Alex Markham is the former
chief executive of Cancer
Research UK, and now a leading
academic at the University
of Leeds. Professor Markham
will play a key role in the
development of arc’s research
programme when he takes up
the post of chairman of the
scientific
strategy
committee in
October this
year.
Paul Rowen,
MP is the
Liberal
Sir Alex Markham
Democrat MP
for Rochdale,
Lancashire, a party Whip and
Shadow Minister for Work
and Pensions covering work,
welfare reform and disability
employment.
Dr Josh Dixey is a consultant
rheumatologist with
considerable experience both
as a medical practitioner and in
the world of developing service
provision and clinical standards
in his past roles as a trustee of
an NHS Trust and of the British
Society of Rheumatology.
Joe Carlebach is a serial
entrepreneur and chairman
of a number of companies,
encompassing the worlds
of information technology,
classical, jazz and world music.
news
New NICE RA guidelines
Scientists have moved a
step closer to their goal of
transforming the treatment
of low back pain by using
adult stem cells taken from
bone marrow to repair
worn discs in the spine.
New guidelines from the
government’s health watchdog
could signal an end to the
current patchiness of care
of rheumatoid arthritis (RA)
patients. In particular, the
referral time from GPs to
specialists should be
speeded up.
Guidelines published by the
National Institute for Health
and Clinical Excellence (NICE)
in February recommend that
GPs should refer patients
with swollen joints that
are not settling down to a
rheumatologist.
If the small joints of the hands
or feet are affected, or if there
has been a delay of three
months between the onset
of symptoms and the patient
seeking medical advice, the
referral should be urgent, say
NICE.
Patients with newly diagnosed
RA should be then offered
a combination of diseasemodifying anti-rheumatic
drugs (DMARDs) including
methotrexate plus short-term
glucocorticoids as a first line
treatment as soon as possible,
ideally within three months
of the onset of persistent
symptoms.
While this already happens
in many parts of the country,
it is by no means standard
practice.
Rheumatologist Dr Chris
Deighton, who acted as a
clinical adviser to NICE in
drawing up the guidelines,
said: “NICE has come to the
conclusion based on the
evidence out there that GPs
need to take advantage of that
narrow window of opportunity
of three months and that we
need to be seeing patients with
RA as quickly as possible.
“For patients who have
early active disease, it’s
not sufficient to give them
methotrexate; treatment needs
to be ramped up quickly,
either at a higher dose or
in combination with other
Scientists edge closer to exciting new
back pain treatment using stem cells
Dr Chris Deighton
DMARDs, and steroids.”
A recent report by the
Rheumatology Futures Group
carried out by the King’s Fund
identified that early RA patients
received “unacceptably wide
variations” of care due to
differences between healthcare
services in the regions.
“Some GPs still wait too long
before they refer RA patients,
and some rheumatologists
still practise a softly softly
approach to DMARDS, but
now an authoritative body like
NICE has said: ‘here are the
standards to which we should
all aspire’,” he added.
Other major recommendations
are that patients should
have access to specialist
physiotherapy to encourage
general fitness and regular
exercise, and learn about pain
relief such as TENs machines.
Patients should also
have access to a multidisciplinary team which
includes occupational
therapists, specialist nurses,
physiotherapists and
podiatrists, and in particular a
named member of the team
who is responsible for coordinating their care.
Dr Deighton said the NICE
guidelines would make it easier
for GPs and rheumatologists
to approach local health
commissioners for more
funding in order to provide
a service that matched the
recommendations.
To read the full NICE RA
guidelines go to: http://www.
nice.org.uk/Guidance/CG79
Low back pain is the
leading cause of disability
in the UK, affecting more
than a million people,
costing the NHS more
than £1bn, and resulting
in lost production and disability
benefits costing a further £1bn
a year.
In most cases low back pain is
associated with degeneration
of the intervertebral disc – soft
tissue that sits between the
bones of the spine and acts as
a shock absorber. With age the
disc loses water and is less able
to resist movement, causing
pain and reducing mobility.
Surgery to remove the disc can
reduce the pain but subsequent
fusion of the vertebrae can
lead to stiffness, restricted
movement and further
degeneration.
Professor Judith Hoyland
Professor Judith Hoyland at the
Tissue Injury and Repair Group
at the University of Manchester
is leading a team funded by
arc, investigating new ways
of regenerating worn discs by
implanting conditioned adult
stem cells to repair the damage.
Within ten years they are hoping
to be able to produce disc cells
from stem cells to inject into
patients, preventing the need for
invasive surgery.
Professor Hoyland and
her team have now received
a further 18 month grant of
£103,000 from the charity
to move from the laboratory
to test the research on a
novel new machine called a
“bioreactor”. The bioreactor is
being used instead of an animal
model because it more closely
mimics the environment found
within the human spine.
Segments of damaged human
lumbar spine will be subjected
to a combination of physical
and biochemical factors in the
bioreactor, together with loads
similar to that experienced by
the spine in everyday life. Stem
cells will then be injected into
the discs to establish whether
they can help to repair the
damage and regenerate the
tissue.
The team will also use this
novel bioreactor to find out
whether blocking the action of
a molecule called IL-1, which
has been shown to be present
in large amounts in damaged
discs, can also reduce or even
halt damage.
“We have shown that we can
turn stem cells from adult bone
marrow into tissue similar to
that in intervertebral discs, and
we are now ready to translate
this lab research into test
systems,” explained Professor
Hoyland. “If it is successful
we will be a step closer to our
aim of using the technique on
patients, without the need for
invasive surgery.”
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7
of lean body mass on BMD as runners had
the highest overall spine bone density.
Lead researcher Dr Pam Hinton, who
is currently working on a long-term
investigation into how well exercise works
to boost bone strength in male osteoporosis
patients, said that exercise plans should
include both resistance and high-impact
activities.
“Exercise programs to increase bone
strength should be designed using what
is known about how bones respond to
exercise,” she said.
“Only the skeletal sites that experience
increased stress from exercise will become
stronger. For example, performing upper
body resistance exercises will not increase
bone mineral density of the hips.”
Dr Hinton went on to highlight activities
such as basketball, volleyball and football
as sports that could potentially increase
BMD. “Any high-impact, dynamic, multidirectional activities result in greater gains
in bone strength”, she concluded.
A spokeswoman for the Arthritis Research
Campaign said: “We suggest that people
High-impact exercise can strengthen bones,
according to the results of a new study
which looked at the activities typically
advised for osteoporosis patients.
Researchers from the University of Missouri
found that activities such as running,
cycling and swimming can increase bone
mass density (BMD), despite the fact that
osteoporosis sufferers are generally advised
to use resistance training to improve bone
strength.
Published in the Journal of Strength
Conditioning, the study considered the
BMD of men aged between 19 and 45. After
making adjustments for body mass index
(BMI), the team found that runners had a
higher spine BMD than cyclists.
Looking at how a lean BMI impacts on
exercise and bone density, the team worked
out the long-term impact of running,
cycling and resistance training. BMD boosts
were found in cyclists and resistancetrainers with a lean body weight.
However the same was not noted for
runners, with the team suggesting that highimpact activity may outweigh the benefits
FLICKR/AFRED
Running 'can benefit bone mass density'
with or at risk of osteoporosis choose
‘weight-bearing’ exercises (any activity which
involves walking or running) which are of
more benefit for bone strength than nonweight-bearing exercises such as swimming
and cycling.”
Obesity increases OA joint replacement risk
Obesity increases the risk of osteoarthritis
(OA) patients needing hip and knee joint
replacements, a new study has revealed.
gain an insight into body fat mass.
A four-fold increase in joint replacement
risk was found in participants with a higher
body weight, BMI and fat mass. The study,
printed in the journal Arthritis Research &
Therapy, also found that fat mass can have
an impact on knee and hip joints up to 15
years after the initial measurements.
A research team from Monash University
in Melbourne, Australia found that a
higher body mass index (BMI) leads to a
higher risk of joint replacement.
Over 32,000 volunteers were involved
in the study which considered the
relationship between fat distribution
across the body, BMI and joint
replacement risk. BMI is typically used as
the indicator for surgery in OA patients,
but the team also looked at waist
measurements and waist-to-hip ratios to
Flavia Cicuttini, lead researcher, explained:
“Adipose mass contributes to increased
joint loading, which may increase the risk
of OA progression and subsequent joint
replacement for severe end-stage OA.
FLICKR/KYLE MAY
“The obesity epidemic occurring in
developed countries is likely to have a
significant impact on the future demands
for knee and hip replacements for OA, and
understanding the mechanism of action will
be important in effective prevention of OA,”
she added.
Professor Alan Silman, medical director of
the Arthritis Research Campaign, said: “The
UK population is ageing and becoming
more obese, and as these are the two major
risk factors for developing ostearthritis, it
is logical to assume that this will have a
considerable impact on the number of joint
replacements being performed.
“Joint replacement surgery is already
Professor Alan Silman
one of the most common types of
surgical procedure, with 65,000 knee
replacements and a similar number
of hip replacements carried out in the
UK every year. If the level of obesity
continues at its current rate the NHS
could be swamped by the need for this
type of surgery.”
Professor Silman added that the report
also highlighted the urgent need for
less invasive surgical techniques that
could be carried out earlier on patients
and so reduce the need for total
joint replacement, such as cartilage
transplantation and, further down the
line, tissue regenerated by stem cells.
8
AFTER ANTI-TNF
What’s next after anti-TNF?
What’s the future for the treatment of rheumatoid arthritis in the wake of anti-TNF therapy
and now, other exciting new drugs? Leading rheumatoid arthritis expert and arc Professor of
Rheumatology at the University of Leeds, Paul Emery, shares his views with Jane Tadman.
T
he Arthritis Research Campaign’s
greatest achievement in its 70
years of existence has undoubtedly
been its pioneering and development of
anti-TNF therapy for rheumatoid arthritis
(RA). Since this new class of drugs first
appeared in the late 1990s, others are now
following, prompting the possibility of – if
not a cure as such – then the prospect of
doctors being able to induce and maintain
patients in a state of remission.
Articles in leading journals like The Lancet
excitedly talk about how remission has
become the goal of managing early
RA, and that this aim needs now to be
included in the design of clinical trials.
The same article also concedes that there
are several definitions of what remission
actually means.
Paul Emery, who has been the lead
investigator in a number of international
Phase III, multi-centre clinical trials of new
RA drugs, explains: “For the first time it is
feasible to talk realistically about remission
as the primary outcome for people with
newly diagnosed arthritis. However, with
more patients achieving a remission state
the definition of remission itself has been
re-examined.
“If we were talking about remission in
cancer, it would mean that you have no
detectable disease and eradication of the
tumour. In RA we conventionally define
remission as clinical remission where there
may still be underlying disease, so we are
now discussing true remission, which is
defined by sensitive imaging (ultrasound or
MRI) and no disease progression over time.
It is still possible to have no symptoms but
yet have significant sub-clinical disease.
Conversely some patients still have pain
but no underlying disease; this is often the
case with patients who are treated late.”
Could the term “being in remission” ever
mean that a patient remains free of disease
– once they have come off drugs? At the
moment, the standard way of inducing
remission is to step up drugs in order to
suppress inflammation. More recently
there has been a change to remissioninduction using anti-TNF as first therapy
in controlled studies and subsequently
to stop it when patients are in remission,
reducing to a maintenance dose of diseasemodifying anti-rheumatic drugs such as
methotrexate.
To Professor Emery, the mere suggestion
that being in remission could mean being
off medication is evidence of how far
treatments for RA have come in the past
AFTER ANTI-TNF
whether they would actually benefit from
such an approach.
Allison Morsali, now
52, developed severe
RA 12 years ago,
and after her
condition failed
to respond
to methotrexate,
she was put on infusions of
infliximab, which also proved
unsuccessful.
A patient first at the early arthritis clinic
in Leeds, then the remission clinic,
Allison’s doctors pushed to get her onto
a second anti-TNF therapy, etanercept.
It has been so effective in controlling
her RA that she and her medical team
are now reducing the dose so that she
can come off the drug completely by
May – and be in drug-free remission.
“I’ve gone from being extremely ill:
taking lots of painkillers and antiinflammatories, wearing splints on
both wrists and having to give up work
for six months, to going back to work
full time, and even going to the gym,
so I’m a shining example of what these
drugs can do,” says Allison, a manager
at a further education college in Leeds.
“I’ve been left with some joint damage
and have restricted mobility, but it’s
been a massive turnaround. Etanercept
few years. “Until recently it would never
have occurred to doctors that remission
would mean that a patient can come off
drugs. That is a huge step forward, but
that’s the way we are going, so there’s
now an evolving definition of the term
remission. At some point it might mean
that a patient is completely well and the
therapy can be stopped.”
The results from several recent clinical
studies have provided evidence of the
effectiveness of anti-TNF in early RA, and
that people with early disease respond
much better than patients with latestage RA. The multi-centre COMET trial
of patients who had had RA for between
three months and two years showed that
50 per cent of them, on a combination
of etanercept and methotrexate, attained
clinical remission after a year, compared to
28 per cent of patients on methotrexate.
Another trial, called TEMPO, showed that
40 per cent and 19 per cent of patients
respectively were in remission after taking
etanercept and methotrexate, but these
patients had had RA for on average seven
years.
Professor Emery has little doubt what
most patients would choose. “If you were
given the opportunity to go into remission
and have a chance to stop your therapy,
but had to take more powerful drugs at
the beginning, would you take it? This
becomes especially relevant when COMET
shows no increase in toxicity. It’s a question
of relative benefit, and RA, true RA, is a
really nasty disease. Anti-TNF makes a
make difference to people’s quality of life.”
Inducing remission in late
stage RA is a real possibility
is the only thing that has controlled my
RA. For the past three years I have been
living a reasonably normal life with the
odd flare.”
Allison has tried once before to give up
medication but flared up after a few
months. However, she feels there has
been such a drastic improvement in her
condition that it’s worth another try.
“I now feel so well and have done for
more than a year – there’s absolutely
nothing wrong with me – and I don’t
think you should keep taking drugs if
you don’t need them.”
“Anti-TNF works in most
people if they are treated
early enough”
Of course, in the UK, such discussion of
inducing remission or treatment of early
RA with anti-TNF therapy remains entirely
hypothetical outside clinical trials. TNF
blockade works in more people with
arthritis when they are treated early
enough, but current guidelines from
the government’s health watchdog the
National Institute for Health and Clinical
Excellence (NICE) mean that only those
people with severe RA who have failed on
at least two DMARDs are eligible for this
class of drugs.
“If cost was not an issue we would be
treating most patients with early RA with
anti-TNF therapy, as the effect is greater
than with standard DMARDs,” says Paul
Emery. “Anti-TNF works in most patients if
they are treated early enough.”
This is not a universal view, and also
begs the question whether it would be
appropriate for all patients with early RA
who have the condition fairly mildly and
Treatment could be even better than it is
and clinical trials have produced better
data than seen in routine clinical practice,
he believes; in other words, there’s a big
lag between trial results and what patients
actually get. However, it should be stressed
that with more than 70 per cent of people
with RA responding well to anti-TNF
therapy in early disease, the possibility of
inducing remission in patients with late
stage as well as early RA is also very real
(see case study).
The argument that putting all new cases
of RA onto anti-TNF therapy would be eyewateringly expensive (the drugs cost about
£12,000 a year per patient) is countered by
the fact that many of these patients would
be able to stay in employment. At the
moment, four out of ten people in work
with RA lose their jobs within five years,
and one in seven give up work within a
year of diagnosis.
9
AFTER ANTI-TNF
New RA drugs in the
pipeline
Tocilizumab:
Expected to be licensed in the UK
in October 2009, the drug is also
currently awaiting NICE approval.
Brand name RoActemra, it is the
first interleukin-6 (IL-6) receptorinhibiting monoclonal antibody
developed for the treatment of RA,
and has a different mode of action
to anti-TNF therapy. Following
several multi-centre Phase III trials
which demonstrated impressive
effectiveness, it is expected to be
licensed for RA patients who fail on
other drugs, including methotrexate
and anti-TNF therapy.
Certilizumab-pegol:
Brand name Cimzia, it is a new antiTNF therapy currently going through
the NICE approval process, with a
decision expected by February 2010.
Phase III trials have shown the drug
effectively prevents joint damage
when combined with methotrexate.
It is already approved in the US for
Crohn’s disease.
Keeping people with RA in work is now
the basis of campaigning by patient
groups, pharmaceutical companies
and professional bodies in the UK,
and almost 50 nursing and medical
organisations have pledged to consider
supporting people of working age to stay
in employment, using job retention as a
critical outcome measure. Paul Emery, as
the next President of the European League
Against Rheumatism (EULAR) from June,
a European body representing patients,
health professionals and research bodies, is
very much involved in this.
He adds: “Anti-TNF is used more widely in
mainland Europe and also in the US, where
there is private medical insurance and
greater freedom for doctors to prescribe,
and certainly NICE is having a major
impact on the use of the therapy in the UK.
But the success of clinical studies showing
the effectiveness of anti-TNF on early RA
will put pressure on NICE to look at this
issue.”
guidance on the “sequential use” of antiTNF therapy. Its previous draft guidelines
had recommended that RA patients who
failed on anti-TNF should not be allowed
to try a second, but the watchdog is now
re-considering the decision in the light of
outcry from campaigning groups.
Paul Emery believes that rheumatologists
should be able to decide on sequential
prescribing. “I wouldn’t try it on everyone,
but we have treated people who had
no response after the first anti-TNF but
then went into remission with another.
However, if you have a patient that has
failed on two anti-TNF therapies you would
be less inclined to treat with a third….”
Whatever the current inadequacies of
the treatment of RA, the strides made
improving it have been massive over the
past 20 years. “Then, if you failed on two
DMARDs, there was nothing else, you just
ran out of drugs,” points out Paul Emery.
“Now we have a greater understanding of
how we can use methotrexate in larger
doses, and of course we have now more
effective treatments like anti-TNF, which
has been the stimulus for other new
drugs.”
Golimumab:
Following positive Phase III trials
results, it is now awaiting licensing
in the USA and Europe for the
treatment of RA, psoriatic arthritis and
ankylosing spondylitis.It has recently
been referred for review by NICE for
methotrexate-naïve RA patients.
Ofatumumab:
Phase III clinical trials into this B-cell
therapy also known as Humax-CD20
are underway, for both methotrexate
and anti-TNF failures. It is also in
long-term trials for non-Hodgkin’s
lymphoma and chronic lymphocytic
leukaemia.
Ocrelizumab:
This drug, which also targets B-cells,
is currently in Phase III trials for
rheumatoid arthritis, lupus and
multiple sclerosis.
The sheer number of new RA drugs
currently in the pipeline could also
pressurise NICE into looking afresh at how
people with early RA should ideally be
treated.
The imminent licensing of another very
promising new RA drug, tocilizumab,
aimed not only at people who have either
failed on or not responded to not only
anti-TNF therapy but also a DMARD such as
methotrexate or sulfasalazine, raises more
interesting questions for NICE. What will be
the pecking order of drugs if tocilizumab
and anti-TNF therapy are the same price,
for example?
Sequential use of anti-TNF
therapy
Another unresolved issue is the so-called
sequential use of anti-TNF drugs. NICE
has decided to review its controversial
He predicts that in another 20 years time
all new cases of inflammatory arthritis
will be rapidly assessed and the concept of
“individualised medicine” will come into
play, with treatment more targeted and
tailored towards individual needs. In the
meantime, he concludes: “We’ve come a
long way!”
• arc’s new clinical studies group
into inflammatory arthritis is
currently discussing the optimal
strategy for patients who fail on
their first anti-TNF therapy, the
best choice of the first biological
drug for RA patients, and how
these drugs can be used most
effectively. A resulting clinical
trial investigating some of these
questions is expected to be
awarded shortly.
SYRINGE IMAGE - JOHN KAPRIELIAN/SCIENCE PHOTO LIBRARY
10
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12
COMPLEMENTARY THERAPIES
Helping patients through the
minefield of complementary
medicines
Ginger – moderate
beneficial effects in
reducing pain
Is there any evidence that
complementary medicines
actually work for people with
arthritis? arc’s new guide
takes a hard look at available
scientific proof.
F
orty-six per cent of the UK
population use complementary
medicines at some point in their
lives, spending more than £450 million a
year on non-conventional treatment.
Among people with arthritis the figure is
even higher – 60 per cent of patients try
such treatments as green-lipped mussels,
homeopathy and rosehip – in a desperate
bid to relieve their pain.
But despite the vast numbers of products
available in health food shops and via the
internet, it can be very difficult for people
to know if what they are taking actually
works – or whether they are simply
wasting their money.
It was in response to this that the Arthritis
Research Campaign decided to produce
the first evidence-based report dedicated
to complementary medicines in arthritis.
The aim was to inform the public whether
there is scientific evidence to support
the clinical effectiveness and safety of
a range of products for which claims
have been made, but in many cases are
unsubstantiated by hard evidence.
The report, Complementary and alternative
medicines for the treatment of rheumatoid
arthritis, osteoarthritis and fibromyalgia
reveals considerable variation in the levels
of scientific information available.
And despite the vast number of
complementary and alternative medicines
on the market, the report found that
evidence from randomised controlled
trials was available for only 40 of them.
Professor Alan Silman, the Arthritis
Research Campaign’s medical
director, explained:
“Complementary
medicines are widely used
by people with arthritis as
they seek to avoid taking
potentially harmful drugs,
preferring natural products.
However, natural does not mean they are
either safe – or effective. Many people
spend hundreds of pounds on these
products and they need to know that
there is a strong chance of benefit.”
Guidance is important
The report covers medicines taken by
mouth or applied to the skin, rather
than therapies such as acupuncture and
chiropractic. It scores medicines according
to their effectiveness with 1 indicating
that the available evidence suggests that
the compound is not effective and 5
indicating that the compound is effective.
It also grades the medicines according to
safety, providing traffic light classifications
for each.
Professor Gary Macfarlane, who led the
research, said it was important that people
with arthritis had some guidance on the
complementary medicines available.
“While over 60 per cent of people with
arthritis or other aches and pains use
some form of complementary and
alternative medicine – and find different
things work for them – it is useful to also
have the scientific evidence available
and just as important to know how safe
we think they are to use,” said Professor
Macfarlane. “All of the evidence can now
be accessed in this definitive report.”
Capsaicin
gel –
extracted
from chilli
peppers
– proved
highly
effective
Fish body oil scores highly
for osteoarthritis
The report throws up several surprises.
For nearly two thirds of compounds used
for rheumatoid arthritis, for example, the
data in the report suggests they don’t work,
while the effectiveness of glucosamine
sulphate, a supplement popular with
people with osteoarthritis, is again called
into question, scoring only 3.
The two highest-scoring products in
terms of reducing pain, movement or
general well-being were fish body oil for
rheumatoid arthritis and capsaicin cream
for osteoarthritis.
Products for osteoarthritis scoring 4 were
herbal extract phytodolor and nutritional
supplement SAMe, while fish liver oil only
registered a 1.
COMPLEMENTARY THERAPIES
What does the report say?
For rheumatoid arthritis (RA):
Nearly two thirds (13 out of 21
complementary medicines [62 per cent])
were shown to have no or little effect
based on the available evidence (scoring 1
out of 5 on the effectiveness scale).
The 13 are: antler velvet; blackcurrant seed
oil; collagen; eazmov herbal preparation;
feverfew; flaxseed oil; green-lipped
mussels; homeopathy; reumalex herbal
mixture; selenium; Chinese herb tong luo
kai bi; vitamins A, C and E anti-oxidant
vitamins; and willow bark.
By contrast fish body oil scored 5 out of 5
for people with RA, reducing joint pain and
stiffness.
For osteoarthritis (OA):
Nearly one fifth (6 out of 27 medicines [22
per cent]) were shown to have little or no
effect based on the available evidence.
Glucosamine, one of the most widely
taken products, showed mixed results
with glucosamine sulphate scoring 3 and
glucosamine hydrochloride scoring 1.
Capsaicin gel, made from chilli peppers,
proved most effective in relieving pain and
joint tenderness, scoring the full 5.
For fibromyalgia:
Only four products were assessed.
None of them highly effective with three
medicines scoring 2 out of 5, and the
fourth an ineffective 1.
Safety:
One quarter of the compounds were given
an “amber” safety classification indicating
there were important side-effects which
had been reported, although there is
much less safety information available for
complementary medicines in comparison
to conventional medicines.
Only one “red” safety classification was
issued against thunder god vine for RA.
Get it here – it’s FREE
Copies of the full 80-page report,
which is free of charge, are available
on 01904 696994 or at
[email protected]
The report is also available on the arc
website at www.arc.org.uk/arthinfo/
documents/6300.pdf
arc’s complementary medicine report – 80 pages of hard facts
Margaret Fisken from
Aberdeen was 40 when she was
diagnosed with rheumatoid
arthritis (RA). For five years
she tried a large number of
complementary medicines to
try and relieve her increasingly
deteriorating condition, spending
around £200 in the process.
“The RA started in my feet and
spread through my body within a
few months,” explains Margaret. “At
that time I wasn’t given any strong
medication, and the disease took hold–
the joints became quite deformed.”
One of the first complementary
medicines she tried was cider vinegar
when she was first diagnosed on
her 40th birthday. “Someone said to
me: ‘I hear such and such works so
you should try it,’ ” says Margaret.
“However, I didn’t find that anything
worked at all.”
Over the years Margaret tried the
following products – without success:
Blackcurrant seed
oil
Capsaicin gel
Chondroitin Devil’s claw Evening primrose
oil Feverfew
Fish oil Ginger Rosehip Glucosamine
Homeopathy Selenium
Vitamins (all) Aloe vera Cider vinegar Echinacea Garlic Green tea
Ginseng Zinc and copper
she found the most helpful
What
have been conventional drugs, in
particular the standard therapy for RA,
methotrexate.
“When the methotrexate
kicked in, I didn’t feel I
needed anything else
so gave up trying the
complementary
medicines,” she says.
“Standard drugs are the only
medicine that has worked for me.
“I was diagnosed in 1992 and between
then and 1998 I was trying everything.
I was virtually chair bound, and
movement was so painful. On occasion,
if going out I had to go around in
a wheelchair and I couldn’t move
without assistance. I was also in severe
pain. Methotrexate revolutionised
my life compared with how I was
before. Within a few months of
starting the medication I improved
fairly dramatically, and it gives me a
reasonable quality of life with just the
odd blip.”
Margaret was a member of the expert
panel convened by arc to assess
products for the complementary
medicines report.
She says she thinks arc’s report is long
overdue and much needed, and is
happy to have been involved. “There
are many people looking to spend large
amounts of money on all this stuff and
people trying to
sell it are hugely
hyping it up,
and yet until
now no-one
has been able
to say with any
authority if it
works or not,”
she adds.
13
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15
PRINCESS MARGARET ROSE ORTHOPAEDIC HOSPITAL/SCIENCE PHOTO LIBRARY
OSTEOARTHRITIS
A new way of looking at osteoarthritis
Acknowledged as one of
the world’s leading experts
in osteoarthritis, Professor
David Felson is promising
a radical new approach to
research and treatment of
the condition, in an exciting
five-year programme of work
funded by arc. Jane Tadman
reports.
Research into developing new treatments
for osteoarthritis have so far failed to
produce anything remotely effective or
safe, as the recent Vioxx drug scandal
showed when a popular painkiller for
osteoarthritis had to be withdrawn
worldwide after a number of related
deaths.
While basic science attempts to chip away
at the many possible causes, hampered
by the fact that essentially osteoarthritis is
not just one disease but several – involving
cartilage, bones, joints and inflammation
– patients struggle to find satisfactory
pain relief, often turning in desperation to
unproven supplements when conventional
medicines fail to work. And while there are
now many drugs on the market that slow
down disease progression in inflammatory
forms of arthritis such as rheumatoid, and
which may even lead to remission in the
not too distant future, a similar drug for
osteoarthritis is acknowledged to be years
away.
So is a completely new approach to
treatment needed? Step forward David
Felson, pictured left, Professor of Medicine
and Public Health at Boston University,
leading world authority on musculoskeletal
diseases, particularly osteoarthritis,
regularly published in leading journals,
principal investigator of the Framingham
Study, one of the biggest epidemiological
studies in the world, and a practising
clinician.
And now he’s heading up research in the
form of a £1.4m special strategic award
for arc looking at ways of developing new
treatment approaches for osteoarthritis.
One of the last unconquered
musculoskeletal diseases
Although the nuts and bolts of Professor
Felson’s research is not due to start until
the summer, he is already spending one
week a month at Manchester University,
where he holds an academic post, and
which he plans to do for the next five
years, overseeing a large multi-disciplinary
research programme and three planned
clinical trials.
“Osteoarthritis remains among the last
unconquered musculoskeletal diseases
and one of the few chronic diseases of
ageing for which there is no effective
strategy to prevent disease progression,”
he says. “And in order to conquer it more
successfully, it needs to be addressed in a
16
OSTEOARTHRITIS
multi-disciplinary fashion. I would never
pretend to study it just by myself, just as
a rheumatologist, I’d only study it if there
were enough folks who have the interest
and the expertise to compliment my own –
radiologists, engineers and biomechanics,
physiotherapists, people who know about
bone and muscle. If you assemble all these
people and pose the right questions and
encourage them to interact and talk with
each other, we can hopefully answer those
questions.”
Bone marrow lesions may
be a cause of pain
Moving away from cartilage
The advent of magnetic resonance imaging
(MRI) which can detect changes in the
joint more accurately than ever before,
has shown that these bone marrow lesions
– areas of bone damage which show
up on MRI as white blotches – are seen
more frequently in people whose knee
osteoarthritis is painful than those whose
knee osteoarthritis is not painful. And the
lesions get bigger when pain gets worse,
suggesting that they are a cause of pain.
What marks out Professor Felson’s
approach as unusual is that he is moving
away from concentrating on cartilage
repair as a central treatment target.
Professor Felson and his group were
among the first researchers to suggest that
despite osteoarthritis being known as a
degenerative condition,
“My own predilection is that
cartilage is maybe not so
important in dealing with and
treating osteoarthritis,” he says. “I
don’t say that it’s not important
in the creation of disease,
but once it’s developed, other
changes occur in the joint and
these then drive the process, and
cartilage takes a back seat. It’s a
radical position, and not generally
accepted at all. One of the reasons I
came to England is that some of the
ideas that underline that position
really emerged here.”
David Felson has reached his
position by watching, with increasing
frustration, a number of treatments
that have been tested and have
failed. “For example doxycycline, (an
antibiotic in the tetracycline family)
which ought to work if cartilage was
the problem, but doesn’t; a trial
of risedronate (a bisphosphonate
drug used to reduce bone loss in
osteoporosis) and a large number
of compounds developed by the
pharmaceutical industry that appear
to stop cartilage loss, but don’t work
in clinical osteoarthritis. We know that
there is no correlation between cartilage
damage on x-rays and pain, because
cartilage has no pain fibres. The research
road is littered with cartilage studies, and
it’s reached a dead end.”
What Professor Felson proposes to
concentrate on instead are treatments that
may both relieve the pain of osteoarthritis
and alter the structures in the joint that
are the sources of this pain, bone marrow
lesions, and synovitis – inflammation of
the synovium, the fluid that surrounds the
joint to keep cartilage slippery.
alleviate pain, and hundreds of people
with osteoarthritis of the knee from the
Manchester area are to be recruited over
the next three years to take part in related
studies.
The other novel idea to be pursued is that
all patients with osteoarthritis do not need
the same treatment, but rather sub-groups
of patients with knee osteoarthritis can
be identified who will respond to targeted
treatment. There are three different
subgroups to be studied. First are those
with patellofemoral osteoarthritis (affecting
the joint between the undersurface of the
knee cap and the femur). Second, there are
those with disease localised to the inside of
the knee and lastly, the team will evaluate
people whose osteoarthritis includes
prominent fluid swelling in their knees.
Targeting people with particular types of
knee osteoarthritis into specific subgroups is an important feature of the
research, although there is inevitably
some cross-over. “I think another
reason why there may be a failure
in the development of treatments is
that people have thought it is a single
disease,” adds Professor Felson. “There
are similar elements in many patients
but for treatment purposes we need
to think of osteoarthritis as a different
group of illnesses that needed to be
treated differently.”
A need for urgent
progress
mild inflammation
also plays a part in the development
of osteoarthritis (which is why antiinflammatories and steroid injections can
be effective). Synovitis is seen in at least
50 per cent of patients with painful knee
osteoarthritis, and previous studies have
shown that if synovitis decreases, so does
pain. So targeting synovitis is another
important strand of the forthcoming
research.
The aim of the research programme is to
evaluate treatments that may affect bone
marrow lesions and synovitis to see if they
In his osteoarthritis clinic in Boston,
Professor Felson takes a multidisciplinary approach to treatment,
offering specific physical therapy
depending on patient’s particular
problems. With ageing and obesity
an even greater crisis on the other
side of the Pond than in the UK,
he is acutely aware of the need
for urgent progress. “I understand
why people take supplements
like glucosamine, even though they
probably don’t work. I don’t try and stop
people from taking supplements because
we need something that helps people and
if they think it helps, then who am I to
know better?”
At the age of 56 Professor Felson is finding
that the subject that has occupied him
professionally for more than 30 years
is also starting to affect him personally.
“I don’t have knee osteoarthritis but I
probably have a mild case of it in my hips,”
he says. “I don’t want to have an x-ray
because I don’t want to know. I know too
much!”
Grants awarded February 2009
Allied health professional
educational training bursaries
Mr David Keene, Physiotherapy
Department, Bristol Royal Infirmary,
Bristol; MSc in advanced manipulative
physiotherapy, £5,000, 13 months.
Mrs Victoria Hill, Physiotherapy
Outpatients Department, Lymington
New Forest Hospital, Lymington; MSc in
neuromusculoskeletal physiotherapy,
£3,185, 24 months.
New national research centre
initiative
Professor Vic Duance, Connective Tissue
Biology Laboratories, Cardiff University,
Biomedical Sciences Building, School of
Biosciences, Cardiff; Arthritis Research
Campaign Cardiff Centre for Biomechanics
and BioEngineering, £2,499,940,
60 months.
Foundation fellowship
Ms Amy Wilson, Department of
Rheumatology, University of Birmingham,
Birmingham; investigating the role of
fibroblast cells in joint destruction in
rheumatoid arthritis, £157,719,
36 months
Dr Paul Bowness, MRC Human
Immunology Unit, University of Oxford,
Weatherall Institute of Molecular Medicine,
John Radcliffe Hospital, Oxford; white
blood cells and immunity in ankylosing
spondylitis, £87,580, 36 months.
Professor Gillian Wallis, Faculty of
Medical & Human Sciences, University
of Manchester, Manchester; how a
faulty gene leads to hip joint shape
abnormalities and early onset
osteoarthritis, £80,530, 36 months.
Professor Sarah Hewlett, Academic
Rheumatology Unit, University of the
West of England, Bristol Royal Infirmary,
Bristol; daily life with rheumatoid
arthritis: patients’ views, management
of symptoms, and deciding what is a
‘flare’, £80,530, 36 months.
Professor David Abraham, Royal Free
Centre for Rheumatology, University
College London, Royal Free & University
College Medical School, Royal Free Campus,
London; how does connective tissue
growth factor stimulate tissue fibrosis in
systemic sclerosis? £86,758, 36 months.
Clinical trials and related studies:
paediatric rheumatology
Dr Paul Brogan, Institute of Child Health,
University College London, Medical School,
London; pilot study into blood vessel
injury in juvenile dermatomyositis,
£30,151, 5 months.
PhD studentships
Dr Rob Layfield, School of Biomedical
Sciences, University of Nottingham
Medical School, Queens Medical Centre,
Nottingham; understanding disease
severity in Paget’s disease, £80,530,
36 months.
Dr Andrew Knight, Institute of Cellular
Medicine, Newcastle University, Faculty
of Medicine, Newcastle-upon-Tyne;
understanding the role of immune B
cells in the development of rheumatoid
arthritis, £80,530, 36 months.
Dr Anwen Williams, Department of
Rheumatology, Cardiff University, College
of Medicine, Cardiff; investigating the
role of a cell surface protein in the
regulation of bone metabolism; a new
target for osteoporosis treatment?
£80,530, 36 months.
Project grants
Professor Anisur Rahman, Centre for
Rheumatology Research, University College
London, Division of Medicine, London;
a new treatment for antiphospholipid
syndrome, £130,763, 24 months.
Dr David Young, Musculoskeletal Research
Group, Newcastle University, School of
Clinical Medical Sciences, Newcastle-uponTyne; understanding the genetic ‘on/
off’ switches that control the activities
of destructive enzymes in cartilage,
£190,051, 36 months.
Dr Pete Smith, Department of Clinical
Dental Sciences, University of Liverpool,
School of Dentistry, Liverpool; is a single
auto-antibody responsible for the wide
range of symptoms associated with
Sjogren’s syndrome? £125,701,
18 months.
Dr Alison Gartland, Academic Unit of
Bone Biology, University of Sheffield,
Musculoskeletal Sciences Section, School
of Medicine, Sheffield; investigating the
role of an important cell surface protein
in the severity of rheumatoid arthritis,
£209,372, 36 months.
Dr Andrew Pitsillides, Department of
Veterinary Basic Sciences, University of
London, The Royal Veterinary College,
London; the interaction between
genetics and joint overuse in the
development of osteoarthritis,
£151,269, 30 months.
Dr Madeleine Rooney, Musculoskeletal
Education & Research Unit, Queen’s
University Belfast, Musgrave Park Hospital,
Belfast; identifying proteins in the blood
that may help to predict disease severity
and outcome in patients with juvenile
idiopathic arthritis, £282,175, 36 months.
Dr Mohini Gray, MRC Centre for
Inflammation Research, University of
Edinburgh, the Queen’s Medical Research
Institute, Edinburgh; investigating the
anti-inflammatory and anti-infection
roles of the alpha-defensin proteins in
arthritis, £214,423, 36 months.
Professor Andrew Rowan,
Musculoskeletal Research Group, Newcastle
University, School of Clinical Medical
Sciences, Newcastle-upon-Tyne; the role of
a key protein pathway in joint cartilage
destruction; new targets for arthritis
therapy? £129,480, 24 months.
Dr Dawn Walker, Department of
Computer Science, University of
Sheffield, Sheffield; the virtual
tendon: a computer-based tool to aid
understanding of tendon function in
health and disease, £155,321, 36 months.
Special strategic award
Professor David Felson, arc Epidemiology
Unit, University of Manchester, School
of Translational Medicine, Manchester;
developing new treatment approaches
for osteoarthritis, £1,460,431, 57 months.
Clinician scientist fellowship
Dr Andrew Filer, Department of
Rheumatology, University of Birmingham,
MRC Centre for Immune Regulation,
Birmingham; predicting diagnosis at the
very beginning of arthritis: the role of
fibroblasts, £482,509, 48 months.
17
KNEE PAIN
Knee pain treatments on trial
Jonathan Hill and Nadine
Foster from arc’s new
national centre for primary
care research explain how
successive clinical trials are
developing better treatment
for people with knee pain.
Many people will experience knee pain
related to osteoarthritis and the numbers are
set to rise, explained in part by our ageing
population and increasing prevalence of
known risk factors such as obesity and poor
physical fitness.
The vast majority of knee problems are
managed in primary care by GPs and
other health care professionals such as
physiotherapists, and yet many people
with knee pain find that the current
NHS services are frustratingly limited.
As a result, researchers at the Arthritis
Research Campaign National Primary
Care Centre at Keele University, through
a series of clinical trials, are trying to
find new ways in which the treatment
of knee pain problems can be
improved.
DAVID MACK/SCIENCE PHOTO LIBRARY
18
ArthritisToday|Spring
Today|Spring2009|www.arc.org.uk
2009|www.arc.org.uk
Arthritis
KNEE PAIN
Teams of researchers at Keele led by
Professor Elaine Hay and Dr Nadine
Foster have conducted two large clinical
trials (funded by arc) of different types of
treatment for people aged 50 and over
who have a clinical diagnosis of knee
osteoarthritis.
Both studies have investigated the
benefits of advice and exercise, which
recent National Centre for Health and
Clinical Excellence (NICE) guidelines
for osteoarthritis (www.nice.org.uk/
CG59) recommend as core treatment,
available to everyone irrespective of age
or level of disability. In the two trials,
NHS physiotherapists provided education,
advice about self-help strategies and pacing
of activities, and exercise therapy. The
exercise treatment was based on a clinical
assessment of the knee problem and
included exercises to strengthen muscles
around the knee, increase patients’ balance
and improve the ease with which everyday
activities can be completed.
NHS network
Since 1999 Dr Jonathan Hill, an arc lecturer
in physiotherapy research at the Keele
centre has helped to establish a network
of NHS physiotherapists who are keen to
collaborate in high quality research such
as large randomised clinical trials. This
partnership between Keele researchers
and clinical physiotherapists has made
these trials possible, and more than 125
physiotherapists from 23 NHS Trusts across
the West Midlands region are now involved.
The physiotherapists not only helped to
recruit and treat patients but were actively
involved in helping to shape the research
questions, develop the treatment protocols,
interpret the results and disseminate the
study findings into NHS practice.
Comparing different trials
The first of these two knee pain trials
called the TOPIK trial (Treatment Options
for Pain in the Knee) evaluated the clinical
effectiveness of two treatment approaches.
The first was a treatment delivered by a
pharmacist working in an enhanced role,
reviewing patients’ medication to ensure
they were taking appropriate tablets for
their pain. The second approach was an
advice and exercise package delivered by
NHS physiotherapists. These two approaches
were compared to a control treatment
that consisted of usual GP care, written
advice and information followed up by
one telephone call by a practice nurse.
The results demonstrated that both the
enhanced pharmacy and exercise package
significantly improved patients’ knee
pain compared to the control treatment.
In addition, the exercise package also
significantly improved patients’ knee
function.
The second knee pain trial known as the
APEX trial (Acupuncture, Physiotherapy
and Exercise for Knee Pain), investigated
the clinical effectiveness of acupuncture in
addition to an advice and exercise package
delivered by NHS physiotherapists. Although
no additional benefit from acupuncture was
found in terms of pain on activity at the
follow-up time points of six and 12 months,
the results for the advice and exercise
package were striking, as the improvements
in patients’ knee pain and function were
greater than those seen in the TOPIK trial.
identifying ways of improving the quality
of, and adherence to, exercise and physical
activity in general. Patients will be recruited
from participating NHS physiotherapy
centres initially for a pilot study in 2009
and then for the main clinical trial in
2010–2011.
So if you have knee
osteoarthritis what should you
be doing about it?
Dr Mark Porcheret, a GP whose research
has focussed on the treatment of knee
osteoarthritis, recommends that firstly
you should be provided with clear advice
about how to manage your condition
from your doctor, and that you should
actively be seeking to improve your
muscle strength and general physical
fitness wherever possible. You may need
the advice and support of a professional
such as a physiotherapist to do this
confidently.
The researchers presented these results to
their physiotherapy collaborators who had
delivered the treatments in order to explore
the reasons why the advice and exercise
package in the APEX trial was more effective
than in the TOPIK trial. The clinicians
suggested that the key difference between
the treatment was the extent to which they
focused attention on making the exercises
more specific and progressive for the
individual and the way in which, overall,
they ‘sold’ the exercise to patients. This
finding suggests that older adults with knee
pain could have a better clinical outcome if
greater attention was given to the quality,
intensity and progression of the exercise
programme.
Other useful treatments include losing
some weight if you need to (as weight
has been shown time and time again
to be linked to the amount of pain
people get in their knee joints), taking
paracetamol (up to two 500mg tablets
four times a day) or using one of the
widely available (from the pharmacist
or your GP surgery) non-steroidal antiinflammatory gels such as ibuleve.
If pain, or problems with mobility
continue, there are a number of other
treatments your GP or physiotherapist
can try, such as acupuncture, stronger
painkillers, local steroid injections,
capsaicin (a cream containing a product
of chilli peppers that gives a numbing
effect) and local heat or cold. If these
are not successful and the problem is
getting a lot worse then surgery may be
the answer.
arc went on to fund Mel Holden through
an Allied Health Professional training
fellowship to work on the Keele ABC-knee
study (Attitudes and Behaviours Concerning
knee pain). This PhD programme aims to
investigate the attitudes and behaviours
of older adults and of physiotherapists to
exercise for knee problems. This research,
alongside other research studies, has
provided useful information that has
identified strategies to improve both the
quality of exercise interventions and ways
to help ensure individuals are supported to
adhere to increased physical activity levels
over the longer-term.
Joint replacement, though involving
major surgery, is very effective but
arthroscopy (where the surgeon
looks inside the joint with a special
telescope) has been shown to only
help a small proportion of people with
knee osteoarthritis: those who have
problems with mechanical locking of the
knee. So remember, even though knee
osteoarthritis is not curable there are
many treatments that can help reduce
pain and increase mobility.
Now recruiting
So NHS physiotherapy partners with Keele
are now being approached by the research
team to collaborate in a third randomised
clinical trial for older adults with clinically
diagnosed osteoarthritis of the knee. This
study is funded by arc and the National
Institute of Health Research (NIHR) and is
called the BEEP trial (Benefit of Effective
Exercise for Knee Pain). The new trial
will investigate the benefit to patients of
•
Dr Jonathan Hill is an arc lecturer in
physiotherapy research, and
Dr Nadine Foster is a senior lecturer
and Department of Health primary
care career scientist at the arc national
primary care centre.
19
20
Back to basics
Newcastle’s arthritis agenda:
a postgraduate focus
A multidisciplinary blend
of basic science and
clinical research drives an
impressively successful
research programme
within the Musculoskeletal
Research Group of Newcastle
University’s Faculty of
Medical Sciences. This
innovative research hub has
established itself as a highly
efficient, patient-focussed
centre that places teamwork
and innovative collaboration
at the forefront of its work
ethos. Arthritis Today looks
at how the first tier of this
thriving academic group, the
postgraduate students, are
progressing across a range of
arc-funded PhD projects.
An impressive reputation
Newcastle University’s Faculty of Medical
Sciences boasts an impressive reputation
for its achievements in strategic planning,
translational research, and academic
teaching. Rated very highly in the recent
2008 Research Assessment Exercise, and
awarded prestigious National Institutes for
Health Biomedical Research Centre status,
the faculty attracts extensive funding
from arc and other bodies, and enjoys
expanding research and clinical research
facilities.
Tim Cawston, Dean of Research and
William Leech Professor of Rheumatology,
sums up a major research emphasis of
the faculty: “It has been said recently that
life expectancy is increasing by five hours
for every single day that passes. What we
PhD students James Locke and Caroline Wilson
need to focus on is: how good will those
five hours be, and how can we make them
better?”
The Musculoskeletal Research Group
certainly rises to this challenge by
promoting a collaborative mix of basic
science and clinical research projects to
address the problems of arthritis and agerelated musculoskeletal diseases, alongside
other specialist areas in paediatric
rheumatology and education research.
Strong interactions between laboratory
and clinical sectors ensure a good supply
of vital clinical samples and excellent
Professor John Isaacs
communication
links that
support their
translational
approach to
disease research.
BACK
TO
BASICS
Up and
coming research in focus
For the PhD students, research is set
against a background of investigative
excellence in a range of disciplines:
immunotherapy, stem cell transplantation,
molecular genetics, and orthopaedic
science, to name just a few. This expertise
and technology supports their approach
to tackling key arthritis issues – identifying
susceptibility and early disease, and
preventing or slowing disease progress.
BACK
TO
BASICS
Immunotherapy and matrix biology are
the main research areas. Immunotherapy
investigates the functioning of the
immune cells in health and disease
and exploits this knowledge to develop
therapies that can restore normal
functioning or block destructive
pathways. Matrix biology is concerned
with the functioning of the cartilage and
bone environment and how molecular
interactions within this dynamic medium
are responsible for cartilage and bone
damage.
Back to basics
Reduced enzymes in
osteoarthritis
Christos Gabrielides is investigating how
cartilage problems in osteoarthritis (OA)
may be caused by defects in cartilage
cell mitochondria. Mitochondria are
small organelles within the cell that are
described as ‘power houses’ because
they generate the chemical power for
cell metabolism. As well as energy,
their chemical reactions produce toxic
substances called free radicals, which
are very reactive and can damage other
molecules.
Christos explains: “We know that
mitochondrial dysfunction plays a role in
OA and other diseases such as Alzheimer’s.
Normally, free radicals are neutralised by
powerful enzymes but we’ve discovered
that in mitochondria from OA individuals,
these enzyme levels are significantly
reduced. We think that free radicals
accumulate and damage mitochondrial
genes, causing cellular malfunction
and eventually cartilage breakdown.
Accumulation of genetic mutations is
believed to be the reason why we age and
since OA and Alzheimer’s generally affect
older people, this may be the cause of
tissue malfunction.”
He aims to investigate the development of
these mutations by studying mitochondria
sourced from OA clinical samples. If the
research confirms that enzyme depletion
increases genetic mutations and OA
progression, it may reveal new targets for
therapy development.
Understanding molecular
recognition
A specific division of immune cells,
called B-cells, are known to play an
important role in the recognition of
microbes when infection occurs in the
body. Recent research suggests that in
rheumatoid arthritis (RA), this defence
system malfunctions and B-cells may
mistakenly recognise some of the body’s
own molecules as ‘foreign’. This results in
the immune system attacking the body–the
autoimmune response.
Caroline Wilson, now in her final PhD
year, has been investigating how B-cells
respond to one of these body molecules,
aggrecan, that makes up much of the joint
cartilage matrix. Aggrecan is an important
component of healthy cartilage and if it’s
attacked by the immune system, cartilage
structure is destroyed.
By investigating the cellular mechanisms
that cause this
recognition system
to go wrong,
Caroline hopes to
produce data that
will contribute to
the development
of drugs designed
to block or even
prevent disease.
“We have generated
a line of B-cells
that recognise only
aggrecan molecules
so that we can
study the detail of the recognition system.
The aggrecan-specific B-cells are 10,000
times more efficient than ordinary B-cells
at inducing an immune response. We’re
using these to characterise the molecular
events that promote autoimmunity.”
Achieving the aggrecan-specific model
has been a large part of her research
and represents a major advance in
autoimmune investigation techniques that
will benefit RA research as well as other
autoimmune disease studies.
Vaccine possibilities for
Dendritic cells feature high on the list of
ground breaking research topics. These
are the immune cells that act like army
generals, issuing orders to the army of
white blood cells and coordinating the
immune response. Some can order an
attack whilst others can suppress an
attack, and it’s this controlling ability
that makes them a key focus for research
purposes.
Media coverage has had the global
research community reverberating with
the news that the Newcastle team, headed
up by Professor John Isaacs and
Dr Catharien Hilkens, had achieved the
first steps in vaccine development for RA
using these unique cells, with arc funding.
Dendritic cells can develop into either the
mature cells that promote the immune
response, or the so-called tolerogenic
cells that prevent immune system
activity. Newcastle researchers take white
blood cells from the patient and subject
them to a novel in vitro technique that
manipulates their differentiation into
tolerogenic dendritic cells. These will
be introduced back into the patient in
vaccine form, by injection directly into an
inflamed knee joint.
It’s hoped that this vaccine system
will suppress or down-regulate the
PhD students Harriet Purvis and Amy Anderson
autoimmune response – using the patient’s
own cells guarantees immune specificity
and there are high hopes for positive
outcomes. Once pilot studies are complete,
larger scale clinical trials will be initiated.
Switching off inflammation
Both postgraduate and postdoctoral
students are engaged in research projects
focusing on this exciting research strand.
One of these students, Harriet Purvis, is
investigating how the tolerogenic dendritic
cells suppress the immune system in RA.
The cells that launch the attack in an
immune response are called T-cells and
recent research has identified a new subset
of these, called Th17 cells. These produce
powerful inflammatory chemicals, or
cytokines, including IL-17 (interleukin-17),
that destroy synovial tissue and enhance
bone destruction.
IL-17 is found in high concentrations in
the synovial fluid of RA joints and it is
suggested that switching off or slowing
down the activity of these ‘bad’ Th17
cells could prevent or inhibit RA. Harriet
explains: “The aim of the project is to learn
how the tolerogenic dendritic cells affect
Th17 cell function. If we can understand
the underlying molecular mechanisms
involved, we may be able to identify new
targets for therapy options. In addition,
we want to identify biomarkers, that is,
molecules that give us some measurable
indication of how well this dendritic
therapy is achieving Th17 cell suppression.
Then we’ll be able to measure treatment
efficacy prior to overt clinical benefit.”
If you would like to read more
about arc’s basic research portfolio,
additional Back to Basics articles can
be accessed on arc’s research website
at www.arc-research.org.uk
21
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The Hints Box
Useful jar opener
I have had rheumatoid arthritis for
38 years and have never, until now,
found a satisfactory jar opener. I have
recently been given the battery-operated
Culinaire One Touch jar opener, which
is wonderful. The company’s details
are: DKB Household Ltd, Bridge House,
Eelmore Road, Farnborough, Hants, GU14
7UE, email cust.serv@dkbrands,co,uk, or
visit their website www.culinaire.com
Janet Oliver, South Brent, Devon
Glucosamine made my foot
and ankle swell up
I suffer from osteoarthritis and have a
hip replacement. I bought glucosamine
as an aid to preventing further arthritis.
I thought you might like to know that
my ankle and foot became very swollen.
I decided to cease taking it, and more
or less immediately my foot and ankle
returned to normal.
Mrs J Wright, Bollington, Cheshire
Where to get mattress
toppers
I have had arthritis for years and have had
both hips replaced in the past three years.
Over the Christmas period I slept in a
bed with a mattress topper. I didn’t know
why it’s so different, and why my body
had stopped hurting in its usual manner
each morning. I was told that the bed
had a mattress topper on the bed. I came
home and ordered one exactly the same
– which is now on my bed with equal
success. I was amazed at the difference it
made in my life. I have never written to a
magazine before but felt I must tell your
enquirer how to purchase this wonderful
item. My mattress topper came from the
White Company (0845 678 8150, www.
thewhitecompany.com) – it is duck
feather and down and for king size
the cost was about £90.
Carol Brister, Kington,
Herefordshire
I recently bought a goose
down/feather mattress topper
from Keys of Clacton (01255
432518) and this has proved very
comfortable for my husband who
has osteoarthritis of the spine. He uses
it on top of a Tempur mattress and he
says that it has greatly helped the pain and
discomfort.
Mrs H Smith, Blandford Forum, Devon
I have dealt with the House of Bath
catalogue (0871 984 2000 www.
houseofbath.co.uk) for many years, and
have always found them very satisfactory.
We bought a mattress topper from them
many years ago and it is still giving good
service.
Margaret Bacon, Sidcup, Kent
A local family department store sells single
duvets for about £6 in their sales. I buy a
single one as it is just the right size to fit
on top of a double bed. I sleep with this
under my sheet and find it a great help.
After a time it becomes rather flat so a
good blow on the line helps to fluff it up
a bit, but after a few years I replace it for
another, which is cheaper than having
it service-washed. I re-use the filling of
the old one by stuffing cushion covers
for smaller supports in chairs. I too tried
manufactured toppers and pillows but I
find this is the most comfortable way for
me, and certainly much cheaper.
J E E Ulliott, Scarborough, North
Yorkshire
Cider vinegar helps keep me
active – at the age of 90
I have had osteoarthritis since my early
sixties (I’m now approaching 90). I have
had two hip replacements and very
23
Views expressed in The Hints Box are those
of readers, and are not necessarily the views
of the Arthritis Research Campaign
stiff knees. I used to be able to walk for
about 20 minutes, or 30 with difficulty,
after which time my back became
increasingly uncomfortable. Then a friend
recommended cider vinegar, which she
had read about in a newspaper. You take
a dessertspoonful in a glass of water, three
times a day. The taste is not more than
mildly unpleasant, but if you prefer, you
can add honey, then it is a pleasant drink.
My health food shop sells Honegar, which
is cider vinegar with honey. The result is
miraculous! I can now walk as much as I
want to. Several of my friends have tried it
with good results, so I warmly recommend
it to your readers.
P J Raikes, Oxford, Oxfordshire
Sympathy for Alice and other
young arthritis sufferers
I am reading The Other Alice, by Alice
Peterson, who not only lost what meant
so much to her – tennis – but suffers
great pain at such an early age. I have felt
great sympathy for those of any age who
suffer from whatever type of rheumatism
or arthritis. I had a successful life as an
athlete, and reading Alice’s book really
brings it home to me how lucky I was for
illness only to catch up with me aged 76
(now 81). The book is so graphic it should
be read by all in government, NICE (what
a misnomer!) consultants, doctors, nurses,
etc, as despite all arc’s work too many
are in ignorance and many who could be
helped are left to suffer.
Miss Jo Ogden, Sleaford, Lincolnshire
Editor’s Note: Another Alice, published by
ICON books is now available in paperback,
priced £7.99.
Seam-free socks?
I wonder if you can help me with a
problem? I have had rheumatoid arthritis
for the last three years and I find that
my feet are very sensitive. In particular I
find the seam on the toe of socks to be
extremely uncomfortable. I have not been
able to find socks that are entirely seamfree. Can anyone help?
Cherry Tugby, Münster, Germany
Send your hints to Jane Tadman, arc,
St Mary’s Gate, Chesterfield,
Derbyshire S41 7TD.
24
Spotlight on Science
Dr Bahaa Seedhom and Professor Vic Duance explain their work in an ongoing series
of questions and answers with arc-funded researchers.
Dr Bahaa Seedhom
What does your work involve?
I must explain that I am now semiretired but work on a part time basis. My
group, which formerly belonged to the
musculoskeletal section led by Professor
Paul Emery has now merged with the tissue
engineering group of the department of
oral biology in the Leeds Dental Institute.
The merger has been a most logical step;
collaboration between our two groups over
the past 15 years has been fruitful, and
resulted in Master and Doctoral theses,
and joint publications in peer reviewed
journals. The collaborative work continues
in exciting translational research in the
areas of tissue engineering (primarily of
ligaments and cartilage) and computer
assisted surgery of joint replacement.
How long has arc been funding you?
arc has generously funded my research
since 1968 – some 41 years, for which I am
most grateful.
What’s the most important thing you
have found out in the past
12 months? And why?
The most important finding was an
observation about the arrangement of cells
in cartilage. Chondrocytes (cartilage cells)
were thought to occur in groups of different
numbers, but the observation, which we
made in bovine cartilage, and published
last year, was that chondrocytes generally
occurred in pairs. The significance of this
pairing may lie in that the cells in a pair
could well be functionally interdependent.
Should this be the case in cartilage of
different species, especially in human
cartilage, it should influence the methods
developed to study the metabolic activities
of chondrocytes. These studies are generally
undertaken on isolated chondrocytes, and
our understanding of their behaviour could
therefore be incomplete, or even incorrect.
As our understanding of chondrocytes'
behaviour is central to the cell based
therapies of cartilage defects, a limited or
incorrect understudying of chondrocytes'
behaviour would render such therapies less
effective.
What do you hope or expect to
achieve as a result of your arc
funding?
arc funding is vital for the continuation of
employment of research colleagues and of
maintaining research projects – without the
flow of finance, projects come to a grinding
halt.
What do you do in a typical day?
As I am not now shackled with any
administrative activities, my work is mostly
research related – supervising research,
participating in writing/editing colleagues’
documents – whether these be papers,
scientific reports or grant applications.
damage and degenerative changes to the
joint that could lead to the development
of the disease. Other studies could help by
suggesting modification to the lifestyle of
folk to keep the joints healthy.
What would you do if you weren’t a
bioengineer?
A profession, which if it did not alleviate
pain would bring joy to people – may be I
would aspire to be a musician, but I would
like to be a consummate one; the life of a
second rate musician is a misery (whereas
that of a second rate scientist is perhaps
more tolerable).
What is your greatest research
achievement?
In the area of prosthetics: a system for
reconstruction of ruptured ligaments.
In the area of applied research:
formulation of a hypothesis on the role of
mechanical factors in the development of
osteoarthritis.
Why did you choose to do this work?
The choice was driven by a desire to put my
engineering skills into use in the medical
field. Human joints and their constituent
structures were an appropriate starting
point; joints are engineering bearings
in every sense except for being living
structures and hence much more complex.
Like many of my fellow bioengineers I
received immense encouragement from
my boss, the late Professor Verna Wright,
who was an innovator and among the most
adventurous in his generation of medical
professionals.
Do you ever think about how your
work can help people with arthritis?
Actually this is what you would habitually
do if you work in this area of research
– nearly all the studies undertaken by
my group have been set up to tackle
an arthritis-related issue. For instance
prosthetic joints are designed to treat
folk at the end stages of the disease with
virtually destroyed joints. Prosthetic
ligaments, as another example, are
intended for the reconstruction of ruptured
ligaments in order to restore stability to
joints. This would hopefully prevent further
About Bahaa
I enjoy listening to classical music:
both live performances and at home,
including much contemporary music,
but I stop when it begins to hurt the
ears. Reading: literature and theological
books. I immensely enjoy constructing
rock and water gardens in the Japanese
style and have built a few. I take
interest in Persian carpets. Renovation
of buildings: trying but the results can
be rewarding at times. Entertaining: I
am reasonably competent at cooking.
Bahaa Seedhom is a reader in
bioengineering at the University of
Leeds.
Spotlight on Science
Professor Vic Duance
What does your work involve?
Cartilage, a tough but flexible tissue, helps
the ends of our bones to glide smoothly
over each other during movement of
the joints, and acts as a ‘shock-absorber’,
protecting the joint from damage during
normal daily life. Collagen molecules
are important to the form and function
of healthy joint cartilage, and damage
to these molecules contributes to the
failure of cartilage in arthritic disease. A
large part of my research career has been
devoted to understanding the structure
and function of the collagens in cartilage,
muscle and the intevertebral discs; tough
tissues that cushion the bones of the spine.
In particular, my research group has been
investigating how collagens change with
age and disease, and how they may also
be involved in the repair of damaged
cartilage. In recent years, our research
emphasis has shifted from collagen itself
to the activities of the cells that make
collagen (and other molecules that form
cartilage). We are interested in how
the complex series of molecular events
that occurs in the cells in response to
mechanical loading during movement of
the joint may sometimes lead to damage
of these molecules, and degeneration
of cartilage. Using this knowledge, our
ultimate aim is to devise strategies for
enhancing cartilage repair in arthritis.
How long has arc been funding you?
Since 1975, I think I have had continuous
arc support for my research, culminating
in the recent award of a £2.5 million grant
to establish a Centre of Excellence for
Biomechanics and Bioengineering here in
Cardiff.
What’s the most important thing
you have found out in the past
12 months? And why?
We have made significant progress in
two areas. We have investigated the
cytoskeleton, a kind of internal framework
that gives the cartilage cell shape and
structure, as well as acting as a ‘telegraph
line’, through which the cell detects and
responds to mechanical loading when the
joint is under pressure. We have found
that vimentin, one of the proteins that
forms the cytoskeleton, differs significantly
between osteoarthritic and normal
cartilage, and that this difference may
influence the way that that the ‘telegraph
line’ responds to loading in osteoarthritic
cartilage. Understanding this complex
process will help us to tease apart the
relationship between mechanical loading,
cartilage damage and the development of
osteoarthritis. We have also been active in
the area of tissue engineering. Repairing
damaged cartilage by implanting new,
healthy cartilage cells from the patient’s
own body is showing some success. Prior to
the repair, some of the damaged cartilage
is first removed; this process causes death
of some of the cells at the removal site,
and we believe that this hinders successful
repair. We have shown that inhibiting
cell death enhances cartilage repair; this
treatment may improve the success rate of
cell implantation procedures.
What do you hope or expect to
achieve as a result of your arc
funding?
A better understanding of the biological
processes that lead to the development
of osteoarthritis, which will enable the
development of better/new targeted drugs
and/or treatments. At present we have very
limited interventions at our disposal to
treat patients. This will be a major drive of
the new centre.
Do you ever think about how your
work can help people with arthritis?
It is easy to forget the over-riding purpose
when undertaking basic research as you
rarely come into contact with patients.
I have always had close association with
clinical colleagues so I don’t believe I have
ever lost sight of “why am I doing this”.
How our research can help patients was
a major consideration in our bid for the
Centre of Excellence for Biomechanics and
Bioengineering, which is an association
of basic scientists from a wide range
of disciplines in collaboration with our
clinical colleagues from rheumatology,
orthopaedics and physiotherapy with both
short and long term goals to help sufferers
of arthritis.
What would you do if you weren’t a
scientist?
Biology was always my main interest in
school and I find it difficult to think what
else I would want to do. Dreams of course
were (and still are) to be a footballer
playing for Manchester United.
What do you do in a typical day?
It would be very nice to say that I go
into the lab and set up experiments on a
regular basis, unfortunately those days are
long gone. I am Director of Postgraduate
Research for the School of Biosciences.
I also have a teaching commitment
involving lectures generally related to my
expertise in connective tissue biology.
What is your greatest research
achievement?
Work over many years from my labs
(Bristol and Cardiff) has made a significant
contribution to our understanding of
the structure and function of cartilage
collagens.
Why did you choose to do this work?
After my PhD in enzyme kinetics I had a
number of options but the opportunity
to investigate the role of collagens in
arthritis was my choice which I have never
regretted.
About Vic
Sport has always played a major
part of my life, football, squash and
running. Football watching (season
ticket holder at Old Trafford) limits
active participation as much these
days, that’s my excuse. I have run six
marathons, and collected sponsorship
for arc on several occasions. However,
I don’t think I could ever run enough
marathons to repay my debt to arc.
Vic Duance is Professor of
Biochemistry at the University of
Cardiff, and director of the new
arc Centre for Biomechanics and
Bioengineering.
25
Questions & Answers
I have had
for the last three
years and I am currently
taking methotrexate and
leflunomide. Last year at the
same time as I had the ’flu
jab I also caught a cold and
I suffered a severe setback
and it took me almost six
months to get back on an
even keel. I'm wondering if
there is any history of the
’flu jab having this sort of
effect – my consultant says
no but I thought I'd ask you.
Can you point me in the right
direction so that I may make
a more informed decision,
because at the moment I am
inclined to forego the jab this
year.
Cherry Tugby, Münster,
Germany
An international
readership! Marvellous.
I often hear similar
stories. A cold (usually) or
‘flu are associated with a
deterioration in the symptoms
of arthritis. Sometimes this is
because their arthritis drugs
are temporarily discontinued
but not always. I assume that
the way the body responds
to the infection is linked to
the way the body causes the
inflammation of arthritis.
For example, several of the
molecules involved in fighting
infection are also involved in
diseases of auto-immunity, like
rheumatoid arthritis. So that is
probably why any infection can
make the arthritis feel worse.
As to your annual ’flu jab,
people on methotrexate and
leflunomide are susceptible
to infections, including ’flu,
and immunisations such
as the ’flu jab are therefore
recommended. My advice is to
try it again next year as there
is no evidence for them doing
harm.
Approximately four
years ago, I fell and
broke five bones in and
around my ankle. Following
surgery and a speedy
recovery, I later developed
arthritis throughout the
ankle area. Obviously,
this was very unpleasant
and painful; particularly
in the cold Canadian
winters. Earlier this year,
I put a whole-house water
filter in my house, which
among other things removes
chlorine from the water. To
my surprise, I have not felt
any arthritic pain since
installing the water filtration
system! To your knowledge, is
the absence of chlorine and
diminished arthritis related? For example, as I write, it is
minus 30 degrees (without
the wind chill), and I have no
pain whatever. Ray Taylor, Moose Jaw,
Saskatchewan
“annual ’flu
jab: people on
methotrexate and
leflunomide are
susceptible to
infections”
Greetings to all those
readers in Moose Jaw! I
have not heard of this
one before. It is well known
that a fracture involving a
joint can lead to arthritis
in that same joint after a
number of years. You sound
to have developed symptoms
of arthritis quite soon after
the accident. I don’t want to
appear sceptical but I wonder
if the symptoms you had in
the ankle following the severe
injuries were due to the trauma
and that these symptoms
have improved with time, as
they do. However, having said
that, the good news is that
your pain is gone and whether
it was time (as I suggest) or
chlorine elimination (as you
propose) doesn’t matter. On
another note, you don’t give
personal details such as age
but has anyone considered the
state of your bones generally?
People living in very northern
latitudes, such as you, are
susceptible to vitamin D
deficiency which can cause a
fall in bone density. Enjoy the
rest of your winter.
As someone who takes
methotrexate for
rheumatoid arthritis I
am concerned at the effect
it has on my hair – thinning
and falling out. Is there
anything that one can take
to minimise this effect of the
drug? Patricia Ranken, Wimbledon,
London
This is an unfortunate
side-effect of
methotrexate therapy.
As doctors we don’t appreciate
how important this is,
especially for women. And
even low dose methotrexate
can cause hair loss to some
extent. The only way to reduce
the side-effect is to reduce the
dose of the drug, as far as I am
aware. However, taking folic
acid on non-methotrexate days
usually helps the other sideeffects and if you are currently
on folic acid just once a week
(as some people are) then it
might be worth taking it on the
six non-methotrexate days.
FLICKR/JAY WOO
26
Dupuytren’s contracture
I read with interest the
letter from Josephine
Knight (Hints Box,
Arthritis Today 142) who
found that glucosamine had
an adverse effect on her
Dupuytren’s contracture. I
take glucosamine and some
nine months ago noticed
that I had a hard lump
forming on the palm of my
left hand, and my GP said it
was the start of Dupuytren’s.
In your opinion, has the
glucosamine caused this?
Should I continue with
the tablet? I would also be
interested to know if you
think Propolis and Royal Jelly
would be of benefit to me. I
have had four successive hip
replacements which have
failed due to infection but
finally seem to be clear.
Mr C Clayton, Spalding,
Lincolnshire
One of the advantages
of growing old, as a
rheumatologist, is that
you begin to experience all
the musculoskeletal diseases
27
Questions & Answers
you have been treating for
years. I am referring to noninflammatory conditions such as
shoulder, knee and back pain,
and osteoarthritis. Now, when I
lecture on these subjects I can
use my own body for illustrative
purposes. I have been known to
get my shirt off during medical
student teaching. This preamble
is just to set the scene for my
answer to you. For some years
I took glucosamine (how could
I not having advocated its use
in this column) and I developed
a Dupuytren’s contracture in
my left hand. (Dupuytren’s
contracture occurs when the
tissues in the palm of the hand
thicken, causing one or more of
the fingers to contract and bend
into the palm. Steroid injections
can be given at an early stage
but surgery may be necessary
later on.)
I didn’t connect the two until
I stopped the glucosamine,
whereupon the Dupuytren’s
contracture improved. This
has been recognised by other
people – see the Dupuytren’s
website: http://www.dupuytrenonline.info/. As to Propolis and
Royal Jelly – I don’t know of
any trial evidence to support
their use but, as I usually say
in this context, it is unlikely to
do you harm. Perhaps, in view
of the above experience with
glucosamine, I should stop
saying this.
I have been taking
methotrexate for seven
years, and recently
the feelings of nausea have
increased and on the day I
take it I feel quite sickly, with
some diarrhoea at times. I
would like some advice on
how this nausea could be
lessened. I do take folic acid
as prescribed. Is there any
food to be avoided or guarded
against on the day I take
methotrexate? I don’t want to
interfere with this medication
which has enabled me to live
a near normal pain-free life
apart from some flare-ups.
Mrs M Slater, Lytham St
Annes, Lancashire
There are four ways of
tackling this problem.
Firstly, as you point out,
folic acid taken on the nonmethotrexate days can help.
There is a trend for people to
take folic acid just once or twice
a week so, if this applies to you,
there is an option of increasing
the dose to six days a week.
Secondly, your doctor or nurse
can give you an additional pill
with Dr Philip Helliwell
to stop the nausea. This need
only be taken on the same day
as methotrexate. Thirdly, if you
are taking methotrexate tablets
there is an option to convert
to methotrexate by injection
– quite a lot of my patients do
this and find it more effective
and less likely to cause sickness.
Fourthly, if all else fails, the
dose of methotrexate can be
reduced, but this may require
you to take additional treatment
to keep your disease under
control.
Send your questions to
Dr Philip Helliwell, arc,
St Mary’s Gate, Chesterfield,
Derbyshire S41 7TD.
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28
king’s college, london
FOCUS ON
KING’S
COLLEGE,
LONDON
since the retirement of previous incumbent
Professor Gabriel Panayi a few years ago.
Professor Frederic Geissmann and Professor Andrew Cope
Top Guys at King’s
The two new arc professors at King’s College, London, talk
to Arthritis Today about their new roles – and their exciting
plans for future research.
There’s nothing modest about Andy Cope
and Frederic Geissmann’s ambitions.
The pair, both newly appointed as Arthritis
Research Campaign professors at King’s
College London (KCL), have big plans for
the future of research into inflammatory
forms of arthritis. In a nutshell, by
combining their clinical and scientific
expertise, they are planning new ways of
tackling inflammation that could lead to
improved treatment – and even prevent
inflammatory disease from happening in
the first place.
With a £4.1m endowment from arc and
input of £2.6m from KCL and Guy’s and
St Thomas’ charity, a new research centre
is being constructed at the heart of the
Guy’s campus where a large group of
scientists and clinicians will collaborate in
a multidisciplinary programme of research
on inflammation and inflammatory
diseases.
The new Centre for Molecular and Cellular
Biology of Inflammation is opening in a
phased way through the year, and should
be fully up and running towards the end
of 2009.
Frederic Geissmann, a world authority on
immune cells called phagocytes, was lured
to KCL with the promise of funding and
freedom to pursue his research interests.
With his impressive CV and research track
record, new colleague Andy Cope describes
him as a “superstar”.
A stimulating environment
Professor Cope in his turn could hardly
resist the offer of being a part of this
new centre from its inception, leaving
his long-time base of the arc Kennedy
Institute of Rheumatology for the promise
of new opportunities for making important
contributions to arthritis research.
Showing visitors around the fledgling unit,
both men are openly excited about the
opportunities that the centre offers them
and their team of up to 70 researchers. It
will provide a stimulating environment for
the next generation of trainee scientists
and clinicians, including the PhD students
soon to be recruited as part of the Oliver
Bird Rheumatism Programme.
They are also keen to stress that the two
of them are very much a package. It’s the
first time that two arc professors have been
appointed at a single institution; Frederic
Geissmann as professor of inflammation
biology, Andy Cope as professor of
rheumatology. They fill a post left vacant
Andy Cope explains the reasoning behind
this: “If you were to go back 20–30 years,
senior academics served multiple roles,
being responsible for the clinical service
and at the same time running a laboratory
dedicated to clinical or basic research. This
would involve significant administrative
duties in the hospital and university
setting, and a big commitment to teaching
and training. It was a challenging job, even
back then. The landscape has changed
in recent years with growing pressures
on clinical service delivery and a highly
competitive research environment. This
has made it very difficult for a clinician
to make major contributions in clinical
medicine and in the laboratory. In fact,
clinical and laboratory-based career paths
in medicine have diverged, and so in
recent years it has become increasingly
difficult for universities to recruit
individuals who can deliver excellence
in all three domains – clinical service,
research and teaching.”
A great opportunity
Frederic Geissmann adds: “This is not
only about spreading responsibilities or
workload. Over the past 30 years, science
has become a major force that has driven
progress in clinical medicine, and there is
a real opportunity today to build a better
clinical medicine based on an in depth
knowledge of the precise, molecular,
mechanisms of diseases. However, only
relatively few universities in the world have
the will and means to lead this process.
So when Adrian Hayday, chairman of the
Division of Immunology, Infection and
Inflammatory Disease (which includes the
academic department of rheumatology)
at KCL, told me that that Professor Alan
Silman, the medical director of arc, and
KCL were keen to give financial support
to create a basic science centre working
on the mechanisms of inflammation
– that would work together with the
rheumatology department to improve our
understanding of chronic inflammatory
diseases, and to develop new diagnostic
markers and better treatments – I decided
it was a great opportunity for me, and I
accepted to be the head of this centre.”
The fruit fly, Drosophila – over 90 per
cent of our genetic material is the same
There are obvious synergies between the
new professors. Professor Cope has been
interested for many years in understanding
how the immune system, in particular
the T lymphocyte, becomes activated
in inflammatory disease, and why the
joint becomes the focus of this activity
in patients with arthritis. Monocytes and
macrophages, the cells whose function
is the focus of Professor Geissmann’s
research, play a central role in immune
activation and are likely to drive the
inflammatory process that attracts T-cells
and other cell types to joint tissues during
the very early stages of disease.
Working towards the ‘Holy
Grail’
Another of Professor Cope’s clinical
research interests focuses on what he
believes is the ‘Holy Grail’ for researchers
and clinicians working in rheumatoid
arthritis research – identifying healthy
people in the community who are most
at risk of developing the condition – and
actually then being able to carry out
studies that might even prevent RA in the
first place.
“The question we now want to ask how is:
can we establish a cohort of apparently
healthy individuals who are at high risk
of developing RA? This would be a great
opportunity to study the interactions
between genes, environmental factors,
and the immune system, and how they
interact to cause disease.”
Treating the high risk group
with cheaper, safer drugs
With collaborators at the arc epidemiology
unit in Manchester and at Imperial
College, Professor Cope is setting up
the first stage, looking to recruit a
substantial cohort of subjects at high risk
of developing RA – for example women
smokers, who may be overweight, and
also carry the genes associated with
susceptibility for RA. The team will then
watch these individuals very closely to see
if they go on to develop the disease, and
compare the results from a low risk cohort
of the same gender and age
but who don’t carry
the susceptibility
genes. Cope believes
that the population
in south east London
is an ideal setting
for such studies.
The ultimate goal
would be to treat the
high risk group with
cheaper and safer
drugs before showing
signs and symptoms
of the disease and
so
prevent it from
Andrew Cope with
occurring.
Tharsana Tharmalingam (research technician) centre and
“The research groups that have made the
biggest impact on patient care have been
those who have invested in building up
large cohorts of patients,” explains Andy
Cope. “A cohort is a large collection of
patients with the same or closely related
disease. By capturing detailed information
from patients and comparing this with
data from healthy control subjects you
can learn a lot about the disease at the
population level.”
Dr Joanna Clark (senior postdoctoral research fellow) right
Professor Geissmann has already gained
valuable new insights into the vital role
that phagocytes play in the inflammatory
response to disease. These cells patrol our
body in the bloodstream and move into
infected tissues when required, engulfing
invading microbes and secreting chemicals
that stimulate other immune cells and
cause inflammation. How do they do this
and why don’t they stop doing this in
arthritis?
To answer these questions, Professor
Geissmann has developed a novel
technique that reveals cell behaviour in
a totally new way. The cells are made to
fluoresce so that they glow when viewed
under a powerful microscope, and are
viewed in real time, in living tissue. The
images are fascinating – the cells can be
seen as blobs of colour moving around the
tissues and interacting with other cells.
Cutting edge imaging
“The methods we use to investigate the
cells are technically very demanding,” says
Professor Geissmann, “and that’s why it’s
so important to have good collaboration
with our imaging department specialists.
We’re using cutting edge imaging and cell
targeting techniques that allow us not
only to view the cells but to investigate
how their development and actions are
controlled.”
Advanced imaging is also generating new
knowledge at the molecular level as well.
Within immune cells, genetic material
is responsible for programming the
manufacture of inflammation chemicals,
such as tumour necrosis factor (TNF) and
other cytokines. Understanding this control
is crucial to inflammation research.
29
with fluorescent proteins so that once
they are activated, the fluorescence can
be tracked using advanced imaging
techniques able to monitor living systems,
and the images are simply stunning.
Professor Geissmann explains: “We want
to find out which genes are responsible
and how they affect the metabolic
pathways that start and stop cytokine
manufacture after infection. In arthritis,
cytokine production is excessive and
sustained. We may be able to design
therapies that interrupt or stimulate the
relevant pathways to prevent this. The
goal is to correct the imbalance without
compromising the body’s ability to fight
infection.”
The role of the humble fruit
fly, Drosophila
The research model for these studies is
the humble fruit fly, Drosophila. This may
seem a surprising model but in fact the
genes responsible for cytokine production
in the fly are similar to those in the human
– over 90 per cent of our genetic material
is the same – and the research will
eventually translate into human studies.
The fly is a very convenient experimental
model – easy to reproduce quickly in
large numbers and without the ethical
constraints of rodent models.
The relevant Drosophila genes are tagged
Christine Wong and Celine Trouillet,
PhD student and laboratory manager
respectively, have been establishing
this novel technique and preparing the
genetic material in preparation for the
studies: “We can’t wait to move into
the new research centre facilities. The
new laboratory facilities have been
purpose-built to our particular research
specifications and will make a huge
difference to our operational ability and
throughput.”
Mapping the outcomes of
the immune response
The flies will be infected with microbes to
stimulate an immune response and the
resulting gene activity tracked in real time.
“We already know,” says Christine Wong,
“that the genes responsible are active in
the joints in humans and interestingly,
this has been found to be the case in
Drosophila too. We are going to study each
Frederic Geissmann with Celine Trouillet and
Christine Wong
gene in turn and map the outcomes of the
immune response for each one.”
Professor Geissmann agrees: “During
infection the body fights to restore health,
and the cytokine system relies on a finelytuned control mechanism. We’ll investigate
how this control is achieved, why the joint
is a focus of activity, and potential avenues
for manipulating the system to block
excessive inflammation in arthritis. The
analysis will be challenging, but we should
achieve the first detailed genetic blueprint
of inflammation control in Drosophila – a
world first.”
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Fundraising – coming events
Fright Nights
If you are looking for an unusual
event or want to get close to some
real ghosts then Fright Nights
events are perfect for you. There
are overnight ghost hunts, ghost
suppers and haunted weekends
with the safe knowledge that
experienced guides, experts and mediums are on
hand. A perfect team event: are you and your colleagues brave enough?
Diving with sharks
Do you have the nerve to come face to
face with a 10ft long sand tiger shark? The
Blue Planet Aquarium near Chester offers
the chance to dive with one of Europe’s
largest collections of sharks. With classes
available for first time divers, this amazing
fundraising opportunity is open to
everyone who has the courage!
Wacky Rally
The Wacky Rally is a banger rally
like no other. Buy a car for no
more than £250, jazz it up with
some wacky decoration and then
drive it through some of Europe’s
most spectacular landscapes, completing
challenges and tasks as you go along and raising vital funds for arc too.
The next rally is to Budapest in
ation
September 2009.
For more inform
these events
of
y
an
r
fo
or to register
246
nd
or Ly sey on 01
or
please call Laura
uk
g.
or
events@arc.
541108 or email arc.org.uk
go to www.
Arctic
Survival
Challenge
The Arctic Survival Challenge is a once in a
lifetime fundraising opportunity to travel to
northern Sweden and test your survival skills. This
adventure (in January 2010) includes the chance to
participate in husky driving, ice fishing, fire lighting,
building shelters and snow holes, cross country
skiing and much more.
CROSS BAY WALK – SATURDAY JULY 4
If you don’t mind getting
your feet wet and enjoy sea
air combined with stunning
Cumbrian coastal scenery – the
Cross Bay Walk should be on
your calendar.
At around eight miles long, the
walk, led by Cedric Robinson
(The Queen’s Guide to the
Sands) takes you from Arnside
across the estuary of the River
Kent to Grange over Sands. The
Cross Bay Walk is suitable for all
ages and there’s even an escape
clause in the form of a tractor
half way across for anyone who
finds the going too much!
For more information about
taking part in this event call
Glenys on 01246 541103.
Support our events in York
The picturesque city of York,
with its famous Minster
and Viking and Roman
connections, also boasts a
successful arc branch, which,
for more than 30 years, has
raised over £250,000. This
year’s fundraising calendar
opens even more opportunities in this great city. Sunday August 2 – York 10k
Run – over 5,000 are hoping
to run the streets of York for
the very first time raising
funds for good causes.
Saturday November 21
– Fundraising Day at
McArthur Glen Designer
Centre.
For more information about supporting these events and the
branch, please contact Kathryn Leverett on 01423 324158/
07736 157802 or email [email protected]
April – arc’s first ever
charity book shop is due
to open in Colliergate.
Sunday July 12 – the York
Rotary Dragon Boat
Challenge along the river
Ouse. Teams of up to 20
people are invited to take
part and raise sponsorship.
FLICKR/LANT
New fundraising ideas
OVERSEAS CHALLENGES 2010
TREK SLOVENIA – June 10-14, 2010
Trek through the hills and valleys of Slovenia, a colourful land
with an untouched natural environment lying on the sunny side
of the Alps.
CYCLE LONDON TO PARIS – June 25-28, 2010
A long weekend cycle challenge from London to Paris, covering
around 300km in three days.
TREK MONT BLANC – August 26-30, 2010
Trek through the Chamonix valley, dominated by the white
majestic dome of Mont Blanc, experiencing breathtaking
mountain scenery and spectacular glaciers.
For more information or to register for any of these events
please call Lyndsey on 01246 541108
or email [email protected] or go to www.arc.org.uk
FLICKR/NOEL COATES
32
Fundraising
Wales weekend
for adventurers
A weekend of challenging
sponsored activities will
take place in June for arc
supporters this year.
Chilly bunnies
Muddy dogs at the ready
Goring and Streatley branch members Sarah
Brownlee and Jane Knight belong to ‘The Muddy
Dog Walking Group’ who, every month, arrange a
sponsored walk and in December raised almost
£200 for arc. However small the event, it serves to
raise the profile of the charity amongst different
people.
It will start off with a Tree
Top Adventure on June 6 in
forests near Betws y Coed in
Snowdonia, North Wales.
Tackling 28 different
elements 50 feet high in the
tree tops, including rope
bridges, rope climbing,
tarzan swings, a zip slide and
culminating in the amazing
freefall leap from a 100 foot
tree top – not for the faint
hearted!
A group of very cold women from Chester le Street
in County Durham, all dressed as Bunny Girls,
took part in a Boxing Day dip in the North Sea
at Sunderland, to raise the profile of a form of
vasculitis called Wegener’s Granulomatosis suffered
by friend and neighbour Andrew Robertson (pictured
on far right, sensibly fully clothed). They certainly
made an impression on the walkers on the beach
and raised over £600 for arc which funds research
into the condition. This is one of several events
planned over the year by this group of supporters,
culminating in participation of the Bupa Great North
Run in September.
Culinary culmination
The next day offers the
Snowdon Challenge: a
hike to the top of Snowdon,
highest point in England and
Wales at 3,560 feet above
sea level. This is a ten-mile
return walk following the
Llanberis Path with the
services of an experienced
mountain guide and lunch
included.
Participants can take part
in either or both events
and spend the weekend in
the spectacular beauty of
Snowdonia National Park.
For a full information pack
and further details contact
arc appeals manager Ruth
Owen now on 01492
518760, 07736 157800 or
email [email protected]
FLICKR/EDWINA BULLOCK
Quilt raffle prizes all
sewn up
Nimble-fingered quilters Marion
Mayrick of Pershore and Jenny
Pegg from Defford in
Worcestershire display the two
quilts and a doll which are the
main prizes in their arc raffle. The
raffle will be drawn at the
Pershore and district branch’s
Christmas Fayre on November 14
2009. For further information
contact Marion Mayrick on
01386 553664.
Get your own copy of
arthritis
Why not introduce Arthritis Today to
someone who you think will benefit
from reading it?
We know that the magazine is passed
on from friend to friend. Why not invite
a friend to obtain their own copy by
completing the coupon? Note that the
coupon applies to NEW READERS only.
It is not a renewal form for existing
donors and does not apply to branch
members.
arthritis
the magazine
reporting research,
treatment and
education
WINTER 2009
No 143
Feet are the
window to
your health
Why podiatry matters
• Ultrasound: better sound and vision
• Osteoporosis – new drugs, same old
lack of awareness
KN
Stalwart of the Wootton Bassett
branch Neil Manley had a double
celebration at the winter coffee
morning in St Bartholomews
Church, Wootton Bassett. He
received a 25-year award from
arc area appeals manager John
Mason and president David Magill
on the same day as his birthday. Yo EE
ur
P
co ten RO
ns m
BL
u
EM
pa ltati inu
ge on te
S
9 o kne ?
n e
25 years of support for
Wootton Bassett branch
A cookery morning with Claire Macdonald: “the
cook for all seasons” at Lavenham Village Hall,
Suffolk, was a huge success, and raised £7,500 for
arc. Mrs Macdonald demonstrated how to cook six
wonderful dishes including venison with chilli and
dark chocolate. The afternoon was completed by
a sumptuous lunch made by the Bury St Edmunds
branch, who then staggered home replete.
arthritis
the magazine
reporting research,
treatment and
education
AUTUMN 2008
No 142
Answering the big research
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To: The Arthritis Research Campaign, PO Box 177,
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• Vitamin D – the sunshine supplement
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34
Fundraising
Having a ball in Cardiff
This year’s Valentine’s Ball in Cardiff was a big success, netting
£7,000 for arc.
Almost 200 people attended the event at Cardiff City Hall and
enjoyed a five course dinner and dancing. Thanks go to those
who attended and sponsors Lidl Cymru, Cottrell Park golf club,
Hammonds Agencies and Julian Hodge Bank.
PHOTO COURTESY OF WESTERN GAZETTE
Among those pictured are (far left, front row) manager of Cardiff
City FC Dave Jones, the Mayor of the Vale of Glamorgan Councillor
Audrey Preston (centre left); managing director of Cottrell Park golf
club, David Johns Powell (back row, red tie); chairman of the arc
Cardiff branch Ann Williams (far right, front row); and arc medical
director Professor Alan Silman (third from left).
Wincanton branch celebration
In the 16 years since it was formed, the Wincanton branch in Somerset
has raised a fantastic £115,000 for arc and, to celebrate, the durable
branch held an evening reception. Local dentist Geoff Worrall, who
raised £5,618 for his sponsored Cycle India Challenge, presented Fergus
Logan, arc chief executive with the resulting cheque. Mr Logan thanked
the branch for all the support over the years, and gave an update on
the work of the charity; he then presented ten-year long-service awards
to sixteen branch members. The evening was rounded off with wine
and delicious canapés generously sponsored by Nigel Case, husband
of the branch chairman. Whilst enjoying the refreshments, Geoff
presented a display of slides from his latest adventure. From left to
right, are chairman Pearl Case, secretary Biddie Lawson, Geoff Worrall,
Fergus Logan and arc area appeals manager Suzie Ladbrooke.
Peak of achievement
Pauline Eastment raised a
magnificent £1,010 by climbing
Mount Snowdon in North Wales
in support of her husband who
suffers from rheumatoid arthritis.
Pauline, from Long Sutton in
Somerset, together with seven
friends, took three hours to climb up the Watkins Path, not the easier
railway line route, to reach the summit of 3,560 feet. After taking
photos and a well-earned rest, it took another three hours to make
their descent.
Firefighters with
iron in their
soul – and their
bodies
Colleagues from
the Royal Berkshire
Fire and Rescue
Service decided to
do the ‘Big One’ –
they entered the
2008 Ironman Triathlon
Contest held in Nurnberg, Germany which is part of the world Ironman
series. This consisted of a 2.1 mile swim, a 112 mile bike ride and a
26.2 mile run, which they did in three relay teams. They raised over
£1,000 for arc from their terrific efforts and pictured, left to right, are
entrants Peter Gray, Pete Briggs, Amanda Clark, Adi Toy, Mat Mansfield
and Dave Geddis.
Bolton’s best
The charity shop in Bolton has
come top in the annual contest
to find the store with the biggest
increase in sales, out of 27 of
arc’s retail outlets. Under the
new management of Liz Livesey,
manager, and Barbara Buxton,
area manager, like-for-like sales
at the Bolton shop went up
by 11 per cent in 2007/8, and
2008/9 started off exceptionally
well, with sales increasing by a
whopping 50 per cent. Shopfitters
Harvey Middleton, who carry out
refits of new arc shop sites and
refurbishments, generously
donated £300 to the winning
shop. Pictured left to right are
Barbara Buxton, area manager
and Liz Livesey, shop manager,
receiving their winning shield
from Leanne Ayris, marketing
manager for Harvey Middleton.
Trouts with clout
The Salmon and
Trout Club is a social
group mostly associated
with the licensed trade,
who meet together a few
times a year over the South
East of England. Most
of them have had, or have some connection with gout – thus, in
cockney rhyming slang, the Salmon & Trout Club. This year they
donated £2,200 from their charity fund to arc, and over the years
their donations have added up to more than £60,000. Pictured are
club members and their mascots: left to right Viv Foss (treasurer),
Jenny Oakshott, arc area appeals manager, Gordon Summers (chair)
and Alan Carter (secretary).
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Arthritis Research UK

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