GOUTTE : COLCHICINE OU CORTICOSTEROIDES

GOUTTE : COLCHICINE OU CORTICOSTEROIDES
QUESTION : Le profil d’effets secondaires de la colchicine rendrait-il ce médicament
moins attrayant dans le traitement de la goutte aiguë ?
AUTEUR : Geneviève Gagnon (MAI 2008)
P
:
toute personne souffrant d’une crise aiguë de goutte
I
:
traitement à la colchicine
C
:
traitement aux corticostéroïdes
O
:
résolution des symptômes avec un minimum d’effets secondaires
CONTEXTE : Lors d’un de mes stages, un médecin me dit que selon lui la colchicine,
est une drogue à éviter vu son profil d’effets secondaires, alors qu’un autre ne jure que
par ce médicament qu’il dit d’une grande efficacité et tout à fait sécuritaire.
RECHERCHE :
Cochrane : avec "gout", je trouve deux revues systématiques qui semblent pertinentes.
« Other reviews » : une revue systématique qui s’intéresse à ma question.
Clinical Evidence (parce que je suis curieuse) : un truc sur le traitement de la goutte
aiguë
Trip Database : on y trouve des recommendations plutôt basées sur des opinions
d’experts. (British society of Rheumatology)
Pub Med : Je ne trouve pas l’étude que je cherche.
RÉSULTATS :
1) Janssens HJEM, Lucassen PLBJ, Van de Laar FA, Janssen M, Van de Lisdonk EH.
Systemic corticosteroids for acute gout. Cochrane Database of Systematic Reviews
2008, Issue 2.
Three head-to-head trials involving 148 patients (74 systemic corticosteroids; 74
comparator drugs) were included. Placebo-controlled trials were not found. In the
studies, different kinds of systemic corticosteroids and different kinds of control drugs
were used, both administered in different routes. Intramuscular triamcinolone acetonide
was compared respectively to oral indomethacine, and intramuscular adrenocorticotropic
hormone (ACTH); oral prednisolone (together with a single intramuscular diclophenac
injection) was compared to oral indomethacine (together with a single placebo injection).
Outcome measurements varied: average number of days until total relief of signs, mean
decrease of pain per unit of time in mm on a visual analogue scale (VAS) - during rest
and activity. In the triamcinolone-indomethacine trial the clinical joint status was used as
an additional outcome. Clinically relevant differences between the studied systemic
corticosteroids and the comparator drugs were not found; important safety problems
attributable to the used corticosteroids were not reported. The quality of the three
studies was graded as very low to moderate. Statistical pooling of results was not
possible.
Authors' conclusions: There is inconclusive evidence for the efficacy and effectiveness
of systemic corticosteroids in the treatment of acute gout. Patients with gout did not
report serious adverse effects from systemic corticosteroids, when used short term.
DONC : Trois études de qualité discutable retenues, pas d’étude randomisée contrôlée,
aucune des trois ne compare un corticostéroïde à la colchicine.
2) Schlesinger N, Schumacher R, Catton M, Maxwell L. Colchicine for acute gout.
Cochrane Database of Systematic Reviews 2006, Issue 4.
One RCT (N=43) comparing colchicine to placebo for the treatment of acute gout was
included in this review. The results favour the use of colchicine over placebo with an
absolute reduction of 34% for pain and a 30% reduction in clinical symptoms such as
tenderness on palpation, swelling, redness, and pain. The number needed to treat
(NNT) with colchicine versus placebo to reduce pain was 3 and the NNT to reduce
clinical symptoms was 2. All participants treated with colchicine experienced
gastrointestinal side effects (diarrhea and/or vomiting) and the number needed to harm
(NNH) with colchicine versus placebo was 1. No studies comparing colchicine to
NSAIDs or other treatments such as corticosteroids or ACTH were identified.
Authors' conclusions: Colchicine is an effective treatment for the reduction of pain and
clinical symptoms in patients experiencing acute attacks of gout, although in the regimen
studied its low benefit to toxicity ratio limits its usefulness. It should be used as a second
line therapy when NSAIDs or corticosteroids are contraindicated or ineffective. More
evidence is needed to compare the efficacy of colchicine to that of NSAIDs or
corticosteroids, the current first line therapy for acute gout.
DONC : Une seule étude randomisée contrôlée (qui date de 1987 : AhernMJ, Reid C,
Gordon TP. Does colchicine work? Results of the first [and last…] controlled study in
gout.). Elle ne compare pas les deux médicaments qui nous intéressent ici, mais
présente des résultats tout de même intéressants.
3) Sutaria S, Katbamna R, Underwood M. Effectivness of interventions for the
treatment of acute and prevention of recurrent gout: a systematic review.
Rheumatology 2006; 45 (11): 1422-1431.
We found 13 randomized controlled trials of treatment for acute gout, two of which were
placebo controlled. Colchicine was found to be effective in one study; however, the
entire colchicine group developed toxicity. The only robust conclusion from studies of
non-steroidal anti-inflammatory drugs is that pain relief from indometacin and etoricoxib
are equivalent. We found one randomized controlled trial, reported only as a conference
abstract, of recurrent gout prevention. CONCLUSION: The shortage of robust data to
inform the management of a common problem such as gout is surprising. All of the
drugs used to treat gout can have serious side effects. The incidence of gout is highest
in the elderly population. It is in this group, who are at a high risk of serious adverse
events, that we are using drugs of known toxicity. The balance of risks and benefits for
the drug treatment of gout needs to be reassessed.
DONC : Parmi les 13 études contrôlées retenues dans cette revue systématique, pas
une seule ne compare la colchicine et les corticostéroïdes. La seule étude qui traite de
la colchicine est celle qui est citée par la revue de Cochrane.
4) CLINICAL EVIDENCE : « Gout »
a) Clinical guide: Colchicine has been used since antiquity to treat gout. A large number
of observational studies support its use. Although it may be efficacious, narrow
benefit to toxicity ratio limits its use in people with gout. Colchicine may be useful in
people for whom NSAIDs and steroids are contraindicated. A dose of 0.5 mg three times
daily may have fewer adverse events than the higher doses commonly used
Both high dose oral NSAIDs and colchicine have a high incidence of adverse events.
Adverse events from occasional short courses of oral steroids are uncommon. For this
reason, oral steroids may be preferable to either NSAIDs or colchicine for the occasional
treatment of acute gout.
DONC : Pas de preuve solide, un guide clinique qui suppose que la colchicine devrait
être évitée en raison de son profil d’effets secondaires.
b) La colchicine, les corticostéroides et les AINS sont cités dans la catégorie « Unknown
effectivness »
Une revue systématique est citée comme analysant l’effet de la colchicine
comparativement aux corticostéroides.
Underwood M. Diagnosis and management of gout. BMJ 2006;332:1315–1319.
Toutefois en lisant le texte on n’y trouve pas d’étude qui compare ces 2 modalités
directement.
5) TRIP DATABASE: British Society for Rheumatology and British Health
Professionalsin Rheumatology Guideline for the Management of Gout.
OBJECTIVE: To develop evidence based recommendations for the management of
gout. METHODS: The multidisciplinary guideline development group comprised 19
rheumatologists and one evidence based medicine expert representing 13 European
countries. Key propositions on management were generated using a Delphi consensus
approach. Research evidence was searched systematically for each proposition. Where
possible, effect size (ES), number needed to treat, relative risk, odds ratio, and
incremental cost-effectiveness ratio were calculated. The quality of evidence was
categorised according to the level of evidence. The strength of recommendation (SOR)
was assessed using the EULAR visual analogue and ordinal scales.
Management of acute gout :
(1) Affected joints should be rested (C) and analgesic, antiinflammatory drug therapy
commenced immediately, and continued for 1–2 weeks (A).
(2) Fast-acting oral NSAIDs at maximum doses are the drugs of choice when there are
no contraindications (A).
(3) In patients with increased risk of peptic ulcers, bleeds or perforations, co-prescription
of gastro-protective agents should follow standard guidelines for the use of NSAIDs and
Coxibs (A).
(4) Colchicine can be an effective alternative but is slower to work than NSAIDs (A). In
order to diminish the risks of adverse effects (especially diarrhoea) it should be used in
doses of 500mg bd–qds (C).
(6) Opiate analgesics can be used as adjuncts (C).
(7) Intra-articular corticosteroids are highly effective in acute gouty monoarthritis (B) and
i.a, oral, i.m or i.v corticosteroids can be effective in patients unable to tolerate NSAIDs,
and in patients refractory to other treatments (A).
DONC : Selon ce groupe d’experts, il faudrait commencer par les AINS.
CONCLUSION :
De toute évidence, il n’y a pas de consensus sur la meilleure approche à suivre pour
contrôler une crise aiguë de goutte. Les preuves restent à faire. La colchicine est
efficace mais tous les patients qui en font usage ont des effets secondaires : douleurs
abdominales, crampes, nausées, diarrhées. Des effets secondaires plus graves
(agranulocytose et autres) sont rapportés lors de la prise à long terme de ce
médicament. De façon générale, on recommande d’initier un traitement aux AINS ou
aux corticostéroïdes d’abord chez les patients qui n’ont pas de contre-indications à la
prise des ces médicaments. Quoiqu’il en soit, un traitement initié promptement après
l’apparition des symptômes semble en réduire la portée et permet une résolution plus
rapide de la crise, qu’il s’agisse d’AINS, de colchicine, de corticostéroïdes ou autre. (On
note ici, parmi les autres traitements possibles : infiltration intra-articulaire de
corticostéroïdes, traitement à l’ACTH IM ou IV, corticostéroïdes IV…) En l’absence de
lignes directrices basées sur des preuves, le fardeau pathologique du patient pourra
nous guider dans le choix du traitement.