Research Summary

Firsekibart Outperforms Colchicine for Preventing Gout Flares During Urate-Lowering Therapy

Edited by:
Ashton L. Stahl

Key Highlights

  • A single subcutaneous dose of firsekibart (100 mg or 200 mg) reduced acute gout flares versus daily colchicine 0.5 mg over 12 weeks in Chinese men with gout initiating urate-lowering therapy (ULT).
  • No acute gout flares occurred in the firsekibart 200 mg group during the 12-week study period.
  • Firsekibart showed a favorable safety and immunogenicity profile, with no treatment-related serious adverse events or discontinuations.
  • Most participants in all groups received febuxostat as their ULT, reflecting contemporary gout management patterns in China.

Published in ACR Open Rheumatology, this randomized, open-label, multicenter, active-controlled phase 2 trial compared firsekibart with colchicine 0.5 mg/day for prophylaxis against acute gout flares during the first 12 weeks of urate-lowering therapy (ULT). The primary objective was to determine whether a single dose of firsekibart could more effectively prevent flares than standard, low-dose colchicine in adults with recurrent gouty arthritis.

The study enrolled adults aged 18-75 years with gouty arthritis, diagnosed according to the 2015 American College of Rheumatology criteria, who had experienced at least 2 flares in the prior year and were planned or had recently initiated ULT. Participants were randomized 1:1:1 to firsekibart 100 mg, firsekibart 200 mg (single subcutaneous injection), or oral colchicine 0.5 mg/day for 12 weeks. ULT (primarily febuxostat 40 mg/day) was started at or just before baseline and adjusted at the investigator’s discretion. The primary endpoint was the mean number of acute gout flares per participant over 12 weeks, defined by prespecified clinical criteria. Safety, secondary efficacy endpoints, and immunogenicity (antidrug antibodies and neutralizing antibodies) were also assessed.

Study Findings

Of 223 screened participants, 162 received study treatment (firsekibart 100 mg, n = 55; firsekibart 200 mg, n = 52; colchicine, n = 55), and 160 completed the trial. All participants were male, with comparable baseline demographics and disease characteristics; mean disease duration ranged from 62.0 to 73.1 months, and ≥ 80% in each group had 2 to 5 flares in the preceding year.

Firsekibart markedly reduced flare risk compared with colchicine. No gout flares occurred in the firsekibart 200 mg group over 12 weeks. In the firsekibart 100 mg group, 1 of 55 participants (1.8%) experienced a single flare, versus 12 of 55 (21.8%) in the colchicine group. The adjusted mean number of flares per participant was 0.02 with firsekibart 100 mg and 0.34 with colchicine, yielding a rate ratio of 0.05 (95% CI 0.01–0.43; P = 0.0060). Between-group differences in the proportion of participants with ≥ 1 flare favored firsekibart (−20.0% for 100 mg and −21.8% for 200 mg vs colchicine).

Flare duration was also shorter with firsekibart: the single flare in the 100 mg group lasted 2 days, compared with a mean of 11.6 days in the colchicine group. A Cox model showed a reduced hazard of flare with firsekibart 100 mg compared with colchicine (HR 0.07; 95% CI 0.01-0.57).

Safety profiles were broadly similar across groups. Treatment-emergent adverse events occurred in 78.5% of firsekibart-treated and 76.4% of colchicine-treated participants, mostly grade 1-2. Grade ≥ 3 treatment-related adverse events were infrequent and comparable (9.3% with firsekibart vs 9.1% with colchicine). No treatment-related serious adverse events, discontinuations, or deaths were reported. Metabolic laboratory abnormalities (hypertriglyceridemia, hypercholesterolemia) and liver enzyme elevations were common in all groups. Antidrug antibodies to firsekibart were low-titer, non-neutralizing, and not associated with safety events or loss of efficacy.

Clinical Implications

According to the study authors, a single subcutaneous dose of firsekibart (100 mg or 200 mg) provided superior prophylaxis against acute gout flares compared with daily colchicine 0.5 mg in Chinese men initiating ULT. The authors note that the reduced flare frequency and shorter flare duration, combined with a favorable tolerability profile and low immunogenicity, support firsekibart as a potential prophylactic option in this setting.

The investigators emphasize that the 12-week follow-up limits the assessment of long-term safety and sustained efficacy, and that the all-male Chinese cohort may limit generalizability to broader populations, including women and non-Chinese patients. They suggest that longer and more diverse studies are needed, as well as trials incorporating intensified ULT strategies and systematic monitoring of serum urate.

Expert Commentary

“The findings in this study suggest that firsekibart may serve as a novel strategy for preventing acute gout flares in patients initiating ULT, potentially transforming the management paradigm for gout,” the researchers concluded.

Reference

Yu Y, Xue Y, Hu J, et al. Firsekibart as a prophylactic treatment for acute gout flare in participants initiating urate-lowering therapy: A phase 2, randomized, open-label, multicenter, active-controlled trial. ACR Open Rheumatol. 2025;7(11):e70111. doi:10.1002/acr2.70111