Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials.
OBJECTIVE
To estimate the efficacy and safety of diacerein as a pain-reducing agent in the treatment of osteoarthritis (OA), using meta-analysis of published randomized placebo-controlled trials (RCTs).


METHODS
Systematic searches of the bibliographic databases Medline, Embase, Cinahl, Chemical Abstracts, Cochrane and Web of Science for RCTs concerning diacerein treatment of OA.


METHODS
explicit statement about randomization to either diacerein or placebo, and co-primary outcomes being reduction in pain and improvement in function. Efficacy effect size (ES) was estimated using Hedges's standardized mean difference. Safety was measured via the risk ratio (RR) of patients having at least one episode of diarrhoea, or withdrawal due to adverse events. Trials were combined by using random-effects meta-analysis. Consistency was evaluated via the I-squared index.


RESULTS
Six trials (seven sub-studies; 1533 patients) contributed to the meta-analysis, revealing a large degree of inconsistency among the trials (I(2)=56%) in regard to pain reduction: the combined ES was -0.24 [95% confidence intervals (CI): -0.39 to -0.08, P=0.003], favouring diacerein. The statistically significant improvement in function (P=0.01) was based on a small amount of heterogeneity (I(2)=11%), but presented a questionable clinical effect size (ES=-0.14). Risk of publication bias could not be excluded, and trials with duration of more than 6 months did not favour diacerein. There was an increased risk of diarrhoea with diacerein (RR=3.51 [2.55-4.83], P<0.0001), and some withdrawal from therapy following adverse events (RR=1.58 [1.05-2.36], P=0.03).


CONCLUSIONS
Diacerein may be an alternative therapy for OA for patients who cannot take paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) because of adverse effects or lack of benefit. However, it is associated with increased risk of diarrhoea, and the symptomatic benefit after 6 months remains unknown.
The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Denmark. emb@frh.regionh.dk
E M
EM
Bartels
H
H
Bliddal
P K
PK
Schøndorff
R D
RD
Altman
W
W
Zhang
R
R
Christensen
D000880:Anthraquinones / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D006801:Humans; D015207:Osteoarthritis, Hip / Q000188:drug therapy*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D010919:Placebos; C025292:diacerein