Background/Purpose: The goal of gout treatment is to reduce serum uric acid (sUA) concentrations below the urate solubility limit. Diacerein is known as an oral IL-1β modulator and also discovered to possess uric acid-lowering effects by inhibiting urate transporter 1 (URAT1). This study was a randomized, placebo-controlled multicenter, 16‑week Phase 2 study designed to test the urate-lowering effects, safety and tolerability of diacerein controlled release tablets (CR), which is designed for bioavailability and pharmacokinetic improvement, and adverse effect alleviation as compared with the currently available immediate-release oral formulation.

Methods: The study comprised 4 periods of 4 weeks each: blinded study medication only, combination with febuxostat 40 mg once daily (QD), study medication plus febuxostat with titration to 80 mg febuxostat QD for those not achieving sUA <6 mg/dL, and finally febuxostat alone. A total of 127 subjects with hyperuricemia and gouty arthritis were randomized to diacerein 100 mg or placebo twice daily (BID). Subjects were Asian, primarily male, mean age 47 years, mean duration of gout 8.7 years, and mean sUA 9.0 mg/dL at baseline.

Results: The study was powered to show a difference in proportion of subjects achieving target sUA <6 mg/dL at Week 8 with significance assessed at a 1-sided p-value <0.05. Significantly more diacerein than placebo subjects (64% vs 55%) achieved the endpoint (p = 0.0337). Also, more diacerein subjects achieved sUA <5 mg/dL at Week 8 (39% vs 27%; p=0.0140). The overall flare rate was not different between groups.

There were no serious adverse events in either group; 6% of diacerein subjects withdrew due to an adverse event. The most common adverse events with diacerein were diarrhea (27%) and soft stools (13%).

Conclusion: This study showed that treatment with diacerein 100 mg BID increased the odds of achieving the clinical sUA target of <6.0 mg/dL at Week 8, after 4 weeks of treatment with diacerein alone and 4 weeks of diacerein in combination with 40 mg febuxostat QD. Treatment with diacerein was shown to be safe and well tolerated with no new safety trends noted in this study. In combination with a low-dose xanthine oxidase inhibitor, diacerein could be a potential formulation to increase the percentage of gout patients who reach the sUA target without increasing flare rates.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-diacerein-controlled-release-tablets-in-serum-uric-acid-reduction-in-treating-subjects-with-gout/