hoofdpijn - Interne Geneeskunde

WAT ALS …
HOOFDPIJN CHRONISCH WORDT?
Prof Jan Versijpt, MD PhD
Kliniek voor Hoofd- en
Aangezichtspijn
Neurologie, UZ Brussel
Stovner, IHC 2009
New daily persistent headache
Primair
= dagelijkse and continue hoofdpijn
•
Secundair
Duidelijk moment van onset met pijn die
onophoudelijk wordt binnen 24u
•
Hoofdpijn sinds > 3 maanden
•
Geen overige aandoening
Subarachnoïdale bloeding
Intracraniële hyper- of hypotensie
•
Post-traumatische hoofdpijn
•
Chronische meningitis
•
Carotisdissectie
•
Sinusthrombose
•
Reuscelarteriitis
•
…
•
•
CHRONISCHE
MIGRAINE
CHRONISCHE MIGRAINE – EVOLUTIE IN
DEFINITIES
ICHD-II published,
defining chronic
migraine
ICHD-III
Pre 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14
ICHD-I
ICHD-I
classification
introduced
ICHD-II-R:
revision of
ICHD-II to be less
restrictive
Chronische migraine - evolutie
• Each year, 2.5% of patients with episodic migraine progress to chronic migraine 1
• Risk factors can be split into: 2,3,4
Modifiable, e.g.
Non-modifiable, e.g.
•
•
•
•
•
•
•
•Age
•Sex
•Race
•Education
•Head injury
Obesity
Depression
Medication overuse
Stress
Caffeine overuse
Snoring
Allodynia
1.Bigal ME, et al. Headache 2008;48:1157–68.
2.Bigal ME, et al. Headache 2006;46:1334–43.
3.Lipton RB. Headache 2011;51:77–83.
4.Bigal ME, et al. Headache 2009;49:S21–33.
Kost in Europa: 27 miljard Euro per jaar
Disability* Class by WHO
*Comparison of the disability of 1 day of a debilitating condition
Increasing disability
Severe migraine
Active psychosis
Dementia
Quadriplegia
Unipolar major
depression
Blindness
Paraplegia
Mild mental
retardation
Down syndrome
Below-the-knee
amputation
Deafness
Disability
Class 4
Disability
Class 5
Disability
Class 6
Disability
Class 7
Menken M. Arch Neurol. 2000;57:418-420.
Medicatie-overgebruikshoofdpijn
Adherence to oral prophylactics for migraine
1. Berger A et al. Poster presented at: The 14th Congress of the International Headache Society; September 10-13, 2009; Philadelphia, PA
PREEMPT study design
 PREEMPT consisted of two Phase III studies of chronic migraine
patients

Largest clinical programme on chronic migraine patients (1384 patients)

Global study across 122 sites in North America (106); and Europe (16)

24-week randomised, double-blind, placebo-controlled phase

32-week open-label phase
Double-blind phase
Weeks
Phone interview
Open-label phase
Baseline
Randomisation
Primary
time point
-4
0
4 8 12 16 20
24
1
2
3
4
5
Treatment
Treatment
Treatment
Treatment
Treatment
28 32 36 40 44 48 52
56
Dodick DW et al. Headache 2010;50:921–936.
BE/0082/2012c Date of preparation April 2012
PROVIDED BY ALLERGAN
The fixed-site fixed-dose injection paradigm
 A total of 31 injections across seven specific head and neck
muscles, with a minimum dose of 155 U of BOTOX® injected per
patient
Occipitalis
Temporalis
(6 x 5 U)
(8 x 5 U)
Frontalis
(4 x 5 U)
Procerus
(1 x 5 U)
Corrugator
(2 x 5 U)
Cervical
paraspinal
group
(4 x 5 U)
Trapezius
(6 x 5 U)
BE/0082/2012c Date of preparation April 2012
PROVIDED BY ALLERGAN
The modified follow-the-pain paradigm
Temporalis (2 x 5 U). Up to an additional two
doses in either the right or left temporalis
muscle, at the points of greatest tenderness
Occipitalis (2 x 5 U). Up to an additional two
doses in either the right or left occipitalis
muscle at the points of greatest pain
Trapezius (4x5 U). Up to an additional four
doses in either the right or left trapezius
muscle at the points of greatest pain
BE/0082/2012c Date of preparation April 2012
PROVIDED BY ALLERGAN
PREEMPT pooled efficacy results (Week 24)
BOTOX®/
BOTOX®
(n=688)
Placebo/
BOTOX®
(n=696)
p value*
Frequency of headache days
–8.4
–6.6
<0.001
Frequency of migraine days
–8.2
–6.2
<0.001
Frequency of moderate/severe headache days
–7.7
–5.8
<0.001
–119.7
–80.5
<0.001
Frequency of headache episodes
–5.2
–4.9
0.009
Frequency of migraine episodes
–4.9
–4.5
0.004
Frequency of acute headache pain medication intake
–10.1
–9.4
0.247
Frequency of triptan use
–3.2
–2.1
<0.001
Total HIT-6 score
–4.8
–2.4
<0.001
Patients with severe (>60) HIT-6 score (%)
67.6
78.2
<0.001
Endpoint
Mean change from baseline in:
Total cumulative headache hours on headache days
Table adapted from Aurora SK, et al. 2011
*p values are from analyses of covariance (ANCOVA) with baseline as covariate. The main effects are treatment and medication overuse stratification.
HIT = headache impact test; MSQ = Migraine-Specific Quality of Life Questionnaire.
1. Aurora SK et al. Headache 2011;51:1358–73
Likelihood of response in initial nonresponders
• Results suggest that patients with chronic migraine, who fail to respond to the
first cycle of BOTOX® treatment, can respond to subsequent treatment cycles
Frequency of headache days: ≥50% firsttime responders*
Percentage of patients, %
Percentage of patients, %
Frequency of headache days: ≥30% firsttime responders*
71.4
9.4
5.4
49.3
11.3
10.3
*First-time responders for a given time point are subjects who never responded at any previous time points. Data are from PREEMPT pooled analysis.
1.Silberstein SD, et al. Poster presented at the 15th Congress of EFNS, September 10-13, 2011, Budapest, Hungary.
.
Possible MoA(s) of BOTOX® on the sensory
systems involved in chronic migraine
• Peripheral sensory effect1,2
–
Blocks release of neurotransmitters associated with peripheral sensitisation of sensory
afferents, such as glutamate and CGRP
• Transcranial afferent effect 3
–
Inhibits transmission in sensory nerves that traverse the cranium and have collateral dural
branches
• Trigeminal-autonomic reflex effect 2,4
–
Inhibition of sphenopalatine (also known as the pterygopalatine) ganglion activation
• Other
MoA = mode of action; CGRP = calcitonin gene-related peptide.
1.Dodick D, Silberstein S. Headache. 2006;46(Suppl 4):S182-S191
2.Aoki KR Headache 2003;43(Suppl. 1):S9–15
3.Kosaras et al. J Comp Neurol 2009;515:331–48
4.Goadsby PJ et al. N Engl J Med. 2002;346:257-270
BOTOX® and head pain
• A study investigated the effect of BOTOX ® in capsaicin-induced head pain
– 14 male volunteers received injections of either saline or 22 U BOTOX®
– Pain was simulated by four intradermal injections of capsaicin (100 µg/ml)
BOTOX® or
placebo
Pre-treatment 24 h
Capsaicin
injection
Day 1
Day 3
Capsaicin
injection
Capsaicin
injection
Figure adapted from Gazerani et al. 2009
1. Gazerani P, et al. Pain 2009; 141:60–9
Day 7 End
Capsaicin
injection
Capsaicin injection
site
BOTOX® injection site
BOTOX® reduced intensity and duration of
capsaicin-induced pain in humans
p<0.001
p<0.001
p<0.001
Saline
BOTOX®
Figure adapted from Gazerani et al. 2009
1. Gazerani P, et al. Pain 2009; 141:60–9
p<0.001
Saline
BOTOX®
p<0.001