Oral diacerein delivers no greater improvement in knee pain compared with placebo for patients with knee osteoarthritis, a randomised trial has found.

The work, from a team of Australian researchers including clinical rheumatologist Professor Catherine Hill, delivers clear evidence against the use of diacerein for these patients, despite some international guidelines still backing its use.

Two hundred and sixty two Australian patients with clinical knee OA, substantial knee pain, and effusion-synovitis on magnetic resonance imaging were randomised to receive either diacerein, 50 mg, once daily or a placebo for two weeks. The dose increased to 50mg twice daily in the treatmnent group if the treatment was tolerated.

At 24 weeks, the treatment group had no greater improvement in knee pain compared with placebo.

The placebo group had a greater decrease in effusion-synovitis volume at 24 weeks (−1.1 mL [placebo] vs 0.4 mL [diacerein] and a greater improvement in quality of life scores.

“This current trial adds in several ways to prior work. It provides high-quality evidence to suggest that diacerein is not an effective treatment for knee OA, even for those with local inflammation,” the authors wrote in JAMA Internal Medicine [link here].

While prior trials had shown mixed findings on diacerein, they had been generally low quality and had not targeted patients with the inflammatory OA phenotype.

Prof Catherine Hill was a co-author of the study.

While pro-inflammatory cytokines like IL-1 have been shown to play a role in synovitis, OA development, and disease progression, to date trials of IL-1 inhibition have been disappointing, the authors noted.

“The limited evidence to date for IL-1 inhibition suggests that IL-1 may not be the right target. While IL-1 plays a key role in OA pathogenesis, it is unclear whether elevated levels of IL-1 in OA are driving disease processes or represent a consequence of the disease itself,” they said.

Medication adherence was lower in the diacerein group, and gastrointestinal side effects were recorded in 41% of treated patients.

The Royal Australian College of General Practitioners already has a conditional recommendation against the use of diacerein in OA, as does the American College of Rheumatology.

However, other international guidelines including European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases recommend its use.

This trial data made it clear the treatment did not have a role to play for these patients, the authors argued.

“These findings do not support diacerein for treating knee pain in patients with knee OA with inflammation,” they said.