Oral diacerein may not improve knee pain compared with placebo in patients with symptomatic knee osteoarthritis and effusion-synovitis on magnetic resonance imaging, according to a randomized clinical trial.
In the multicenter double-blind trial, researchers evaluated whether the interleukin-1 beta inhibitor diacerein could reduce knee pain in patients with knee osteoarthritis (OA) and effusion-synovitis detected on magnetic resonance imaging (MRI), a marker of joint inflammation associated with worse symptoms and structural progression.
The researchers randomly assigned 262 adult patients with symptomatic knee OA and substantial knee pain to receive diacerein or placebo for 24 weeks across four centers in Australia. The mean age was 54.9 years, and 56% of the participants identified as female. The participants had baseline knee pain scores above 40 mm on a 0 to 100 visual analogue scale (VAS) and imaging evidence of effusion-synovitis.
The patients received 50 mg of diacerein or placebo once daily for 2 weeks followed by escalation to 50 mg twice daily if tolerated. The primary outcome was a change in knee pain on the VAS over 24 weeks, with a minimal clinically signficant difference defined as 15 mm.
At 24 weeks, both patient groups experienced similar reductions in knee pain. Mean VAS scores decreased by 19.9 mm in the diacerein group and 18.6 mm in the placebo group, yielding a between-group difference of −1.3 mm.
Secondary outcomes showed broadly comparable results between the groups. Western Ontario and McMaster Universities Osteoarthritis Index pain scores decreased by 77 points in the diacerein group and 70 points in the placebo group, while function scores improved by 253 points and 234 points, respectively.
MRI findings also failed to demonstrate structural improvement with treatment. Effusion-synovitis volume increased slightly in the diacerein group by 0.4 mL but decreased by 1.1 mL in the placebo group, producing a between-group difference of 1.5 mL.
In addition, quality-of-life measures favored placebo. Scores on the Assessment of Quality of Life instrument improved by 0.07 in the placebo group compared with 0.03 in the diacerein group.
In responder analyses, 58% of the patients receiving diacerein met Outcome Measures in Rheumatology–Osteoarthritis Research Society International response criteria compared with 54% of those in the placebo group.
Subgroup analyses examining inflammation severity, neuropathic pain characteristics, radiographic joint space narrowing, depression, and fibromyalgia showed no statistically significant differences in treatment response across the categories.
Treatment adherence differed modestly between the patient groups. Overall, 75% of the participants took at least 80% of study medication, including 82% in the placebo group and 67% in the diacerein group. A per-protocol analysis limited to adherent participants produced similar results to the primary analysis.
Adverse events occurred more frequently with diacerein. For instance, gastrointestinal symptoms were reported in 42% of the patients receiving the drug compared with 25% of those receiving placebo. Diarrhea was the most common event, affecting 39% of the patients in the diacerein group vs 22% of those in the placebo group. Changes in urine color occurred in 10% of the patients receiving diacerein and 0% of those receiving placebo. One serious adverse event, colonic pseudo-obstruction, was reported in the diacerein group.
The researchers noted several limitations. Eligibility required MRI evidence of effusion-synovitis, but imaging was performed without contrast, which prevented differentiation between synovial thickening and joint effusion. The findings may also not generalize to patients without inflammatory features of OA.
Despite targeting patients with an inflammatory phenotype thought most likely to benefit from anti-inflammatory therapy, the drug failed to improve symptoms.
“In this randomized clinical trial in patients with symptomatic knee OA and effusion-synovitis on MRI, diacerein (50 mg, twice daily) over 24 weeks resulted in no greater improvement in knee pain compared with placebo,” wrote lead study author Dawn Aitken, PhD, of the Menzies Institute for Medical Research at the University of Tasmania in Australia, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: JAMA Internal Medicine