Background Diacerein is currently registered as a drug for the treatment of osteoarthritis. Evidence from in vitro studies and animal models of rheumatoid arthritis (RA) [1–3] suggest that it may also be a treatment option in early RA.
Objectives To evaluate the efficacy and safety of diacerein in early RA patients with inadequate response to methotrexate (MTX).
Methods Active early RA patients, according to the 1987 ACR revised criteria for RA, were invited to join this randomised, double-blind, placebo-controlled, multicentre phase II study. Inclusion criteria were insufficient response to MTX (≥7.5 mg/week), <2 years disease duration, DAS28 >4.0, tender joint count ≥6/68 and swollen joint count ≥6/66. After a one-month run-in period on stable MTX therapy, eligible patients were randomised to receive either diacerein (DAR) 50 mg or matching placebo (PBO) twice daily in addition to MTX. Study assessments were scheduled at baseline (W0), then every 4 weeks through 24 weeks of treatment (W24). The primary endpoint was the ACR20 response criteria at W24. Secondary endpoints included EULAR response criteria for RA, MCII (≥15 mm improvement in pain on VAS) and PASS (<41 mm of pain on VAS) response criteria.
Results On 45 patients screened, 40 were randomised (ITT data set), and received at least one dose of study medication (safety data set). Five patients prematurely discontinued the study due to consent withdrawal (DAR: 2; PBO: 1) or unacceptable increase in disease activity (DAR: 2). Both groups were homogeneous at baseline for demographic and disease characteristics, except for a lower tender joint count in the DAR group (16.5±8.8 vs 24.6±13.2, p=0.0220). The efficacy analysis performed on the ITT data set showed that all parameters improved throughout the study in both groups. At W24, 13 patients in the DAR group and 9 patients in the PBO group responded to the ACR20 criteria (p=0.2036), while 15 patients in the DAR group reached a good or moderate EULAR response vs 5 patients in the PBO group (p=0.0016). The DAS28 improved from baseline by 1.26±1.37 and 0.85±1.17 in the DAR and PBO groups, respectively (p=0.1199). At W24, the MCII was met by 13 patients in the DAR group vs 9 patients in the PBO group (p=0.0388), while 16 and 10 patients reached the PASS, respectively (p=0.0014). Rescue medication consumption (paracetamol) was similar in both groups. The sensitivity analysis performed on the per protocol set (DAR: 19; PBO: 20) confirmed the results of the primary analysis.
Thirty-one patients reported one or more adverse events (DAR: 16, PBO: 15). The most frequent adverse event (AE) was chromaturia (DAR: 8, PBO: 2), followed by diarrhoea (DAR: 4, PBO: 4) and upper respiratory tract infection (DAR: 2, PBO: 5). Gastrointestinal disorders accounted for 37.5% of all AEs (DAR: 8, PBO: 7). One serious AE was reported in each group (DAR: hip fracture; PBO: pharyngotonsillitis); both were not related to the study medication.
Conclusions Diacerein 100 mg was shown to have efficacy in reducing RA signs and symptoms when combined with MTX. However, more powered clinical trials are needed to confirm these pilot findings.
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Disclosure of Interest None declared