Firsekibart versus compound betamethasone in acute gout patients unsuitable for standard therapy: A randomized phase 3 trial.

This phase 3 trial evaluated the efficacy and safety of Firsekibart, a novel, fully human anti-interleukin-1β monoclonal antibody, in patients with frequent acute gout flares unsuitable for standard therapy. Patients were randomized (1:1, stratified by baseline pain visual analog scale [VAS]) to the Firsekibart (200 mg) or compound betamethasone (CB; 7 mg) group. Co-primary endpoints included change in pain intensity in the target joint at 72 h (non-inferiority testing) and time to first new flare within 12 weeks (superiority testing). The non-inferiority margin was 10 mm. The full analysis set included 311 patients (Firsekibart: N = 156; CB: N = 155). At 72 h, the least squares mean change in pain VAS scores from baseline was -57.09 mm (95% confidence interval [CI]: -60.08 to -54.10) for Firsekibart and -53.77 mm (95% CI: -56.77 to -50.77) for CB, with treatment difference of -3.32 mm (95% CI: -7.56 to 0.91), establishing non-inferiority. The median time to first new flare was not reached within 12 weeks in the Firsekibart group compared with 45.0 days (95% CI: 28.00 to 63.00) in the CB group. Firsekibart significantly reduced the risk of new flare by 90% vs. CB (hazard ratio: 0.10; 95% CI: 0.06 to 0.17; stratified log rank p < 0.0001). Efficacy was consistent across subgroups. Treatment-emergent adverse events occurred in 71.2% of Firsekibart-treated patients and 69.9% of those receiving CB. In conclusion, Firsekibart is effective and well tolerated for acute gout flares in patients unsuitable for standard therapy, demonstrating non-inferiority in rapid pain relief and significant superiority in preventing flare compared with CB.