Efficacy and Safety of Firsekibart Compared to Etoricoxib for Gout Flares: A Phase 2, Multicenter, Open-label, Active-controlled, Randomized Non-inferiority Trial

Firsekibart, an anti-interleukin (IL)-1β monoclonal antibody, has demonstrated more sustained control of gout flares compared with compound betamethasone in previous clinical studies. This study evaluated the efficacy and safety of firsekibart versus etoricoxib for the treatment of frequent gout flares. In this phase 2, randomized, open-label, active-controlled, multicenter study (NCT05936268), adults with gout according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) 2015 criteria experiencing frequent flares (≥ 2 flares within 12 months pre-screening) were randomized (1:1) to receive either a single subcutaneous injection of firsekibart 200 mg, or once-daily oral etoricoxib 120 mg administered until pain remission or treatment intolerance for up to 8 days. The primary endpoint was change from baseline in target joint pain intensity (0–100 mm visual analogue scale [VAS]) 72 h post-treatment. Non-inferiority (margin: 10 mm) was assessed first; if achieved, superiority was subsequently evaluated. Safety was also evaluated. Overall, 123 patients received firsekibart (n = 61) or etoricoxib (n = 62). Firsekibart was non-inferior and superior to etoricoxib in change from baseline in target joint pain VAS scores at 72 h post-treatment (difference: − 10.91 mm; 95% confidence interval [CI]: − 18.11, − 3.72). Treatment-emergent adverse events (TEAEs) occurred in 77.0% (n = 47) and 51.6% (n = 32) of patients receiving firsekibart and etoricoxib, respectively. The most common TEAE in both groups was hypertriglyceridemia. No TEAEs led to treatment discontinuation or study withdrawal, and no treatment-related serious adverse events (AEs) or deaths were reported. Compared with etoricoxib, firsekibart provides superior target joint pain relief and is well-tolerated in patients with frequent gout flares. ClinicalTrials.gov identifier: NCT05936268; date of registration: 7 July 2023.