Background/Purpose: There is an unmet need for treatments of knee OA. Diacerein is recommended for alleviating pain in OA patients for its anti-inflammatory effect by blocking interleukin-1β. Previous trials showed a small beneficial effect of diacerein on pain and joint space narrowing (JSN) in OA patients. However, none specifically targeted patients with an inflammatory OA phenotype who might benefit most from this therapy. Therefore, this trial aimed to determine the effect of diacerein on knee pain and effusion-synovitis over 24 weeks in patients with symptomatic knee OA and MRI-detected effusion-synovitis.

Methods: The DIaCerein for Knee osteoarthritis with EffusioN-Synovitis (DICKENS) study was a multicentre, randomised, double-blinded, placebo-controlled trial over 24 weeks. Patients aged 40-64 years who had significant knee pain (defined as a 0-100mm visual analogue scale (VAS) ≥ 40 mm) and MRI-detected effusion-synovitis were randomised to receive either diacerein (50 mg twice daily for the first 2 weeks, increasing to 100 mg twice daily afterwards if gastrointestinal side-effects acceptable) or identical placebo. Those with severe knee OA (Grade 3 JSN using the Osteoarthritis Research Society International (OARSI) atlas) were excluded. The primary outcome was improvement in knee pain on a 0-100mm VAS at 24 weeks. Secondary outcomes included improvements in effusion-synovitis, knee pain, function, and stiffness by the WOMAC, leg strength, and quality of life (the Assessment of Quality of Life (AQoL-8D) and the 5 level EuroQoL-5-dimensional version (EQ-5D-5L)). Pre-specified stratification analyses were conducted by effusion-synovitis (grade 1 or 2/3) at baseline.

Results: 262 patients (mean ± SD age 54.9±6.1 years, 147 females) were enrolled, and 88.5% completed the trial. At baseline, mean ± SD knee VAS pain (0-100) was 54.8±18.3, and median (interquartile range) effusion-synovitis volume was 4.6 (2.3 to 9.8) ml. After 24 weeks, there was no significant difference in changes in knee pain (VAS pain: -19.9 vs -18.6, p=0.77; WOMAC pain: -76.9 vs -70.4, p=0.64) or WOMAC function (-253.2 vs -234.0, p=0.68) and stiffness scores (-37.5 vs -31.4, p=0.34) between the diacerein and placebo groups. Between-group difference in change in effusion-synovitis volume was statistically significant (diacerein vs placebo: +0.4 ml vs -1.1 ml, p=0.002). There were no significant between-group differences in other secondary outcomes, except that improvement in AQoL-8D (0.03 vs 0.07, p=0.02) was significantly higher in the placebo group. Pre-specified analyses showed no between-group differences in change in knee symptoms in patients with either grade 1 or 2/3 effusion-synovitis at baseline. Adverse events were more frequent in the diacerein group, especially diarrhoea (38.6% vs 22.3%) and coloured urine (10.6% vs none).

Conclusion: In patients with symptomatic knee OA and effusion-synovitis, 50-100 mg twice daily of diacerein, compared to placebo, did not significantly improve knee pain or effusion-synovitis over 24 weeks. These findings do not support the use of diacerein in treating patients with knee OA and effusion-synovitis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dickens-a-multicentre-randomised-controlled-trial-of-diacerein-for-knee-osteoarthritis-with-effusion-synovitis/