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Evidence summaries

Diacerein for Osteoarthritis

Diacerein may have a minimal beneficial effect in osteoarthritic pain and may slow the progress of osteoarthritis in the hip, but this effect is of questionable clinical relevance. Possibility of severe diarrhoea and liver toxicity limit the use ov diacerein. Level of evidence: "C"

The quality of evidence is downgraded by study quality (incomplete outcome data) in approximately 80% of the studies, and unclear allocation concealment.

A Cochrane review [Abstract] 1 included 10 studies on diacerein for treatment of osteoarthritis, with a total of 2 210 subjects. Diacerein is an interleukin-1 inhibitor found in plants of the generus Cassia. Its active diacetyl derivative, rhein, is an anthraquinone with moderate anti-inflammatory and analgesic activity and weak laxative effects.

Evidence from six trials (1 283 participants) indicated that diacerein has a small beneficial effect on overall pain (measured on a 100 mm visual analogue scale) at three to 36 months (MD -8.65, 95% CI -15.62 to -1.68), which is equivalent to a 9% pain reduction in the diacerein group (95% CI -16% to -2%) compared with the placebo group. This benefit may not be clinically significant.

No statistically significant differences in physical function (4 studies, 1006 participants) were noted between the diacerein and placebo groups (Lequesne impairment index, 0 to 24 points) (MD -0.29, 95% CI -0.87 to 0.28).

Evidence from two trials (616 participants) on slowing of joint space narrowing (a decrease greater than 0.50 mm) in the knee or hip favoured diacerein over placebo (RR 0.85, 95% CI 0.72 to 0.99), with an absolute risk difference of -6% (95% CI -15% to 2%) and NNTB of 14 (95% CI 8 to 203). Analysis of the knee joint alone (1 study, 170 participants) did not reach statistical significance (RR 0.94, 95% CI 0.51 to 1.74).

None of the trials of diacerein versus placebo measured quality of life. According to one trial (161 participants), which compared diacerein versus non-steroidal anti-inflammatory drugs (NSAIDs), the quality of life of participants in the two groups (as assessed by the Short Form (SF)-36 health survey questionnaire (0 to 800 sum score)) did not differ significantly (MD -40.70, 95% CI -85.20 to 3.80).

Low-quality evidence from seven trials showed significantly more adverse events in the diacerein group compared with the placebo group after two to 36 months, mainly diarrhoea (RR 3.52, 95% CI 2.42 to 5.11), with an absolute risk increase of 24% (95% CI 12% to 35%), and a number needed to treat for an additional harmful outcome (NNTH) of 4 (95% CI 3 to 7).No statistically significant differences in participant withdrawal due to adverse events were seen at two to 36 months for diacerein compared with placebo (RR 1.29, 95% CI 0.83 to 2.01).

Note: On 19 March 2014, the Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) endorsed recommendations to restrict the use of diacerein-containing medicines in order to manage the risks of severe diarrhoea and effects on the liver.Due to the risks associated with severe diarrhoea, diacerein is no longer recommended in patients aged 65 years and above. It is also advised that patients start treatment on half the normal dose (i.e. 50 mg daily instead of 100 mg) and should stop taking diacerein if diarrhoea occurs.

    References

    • Fidelix TS, Macedo CR, Maxwell LJ et al. Diacerein for osteoarthritis. Cochrane Database Syst Rev 2014;(2):CD005117. [PubMed]

Primary/Secondary Keywords