Osteoarthritis and Cartilage
Volume 18, Issue 3 , Pages 289-296, March 2010

Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials

  • E.M. Bartels

      Affiliations

    • The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Denmark
    • Copenhagen University Library, Denmark
    • Corresponding Author InformationAddress correspondence and reprint requests to: Else Marie Bartels, The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, DK-2000 F, Denmark. Tel: 45-38164198; Fax: 45-38164159.
    • ,
  • H. Bliddal

      Affiliations

    • The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Denmark
    • Center for Sensory-Motor Interaction, Aalborg University, Denmark
    • ,
  • P.K. Schøndorff

      Affiliations

    • The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Denmark
    • ,
  • R.D. Altman

      Affiliations

    • David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USA
    • ,
  • W. Zhang

      Affiliations

    • Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, UK
    • ,
  • R. Christensen

      Affiliations

    • The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Denmark
    • Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Denmark

Received 3 June 2009; accepted 9 October 2009. published online 02 November 2009.

Summary 

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. Inclusion criteria: 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 (I2=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 (I2=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.

Key words: Diacerein, Placebo, Osteoarthritis, Knee, Hip, Meta-analysis

 

PII: S1063-4584(09)00278-7

doi:10.1016/j.joca.2009.10.006

Osteoarthritis and Cartilage
Volume 18, Issue 3 , Pages 289-296, March 2010