POS1177 EFFICACY AND SAFETY OF FIRSEKIBART IN ACUTE GOUTY ARTHRITIS: A MULTICENTRE, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, ACTIVE-CONTROLLED PHASE III STUDY

Background: Acute gouty arthritis is a common and debilitating condition, especially for patients who are contraindicated for, intolerance of, or unresponsiveness to NSAIDs and/or colchicine. IL-1 inhibitors are a promising approach while available drugs are limited. There is an urgent need to explore more alternative therapies. Objectives: We introduce the efficacy and safety data of Firsekibart for the treatment of acute gouty arthritis, representing the first phase III clinical trial of an IL-1β monoclonal antibody for acute gout flares conducted in China. Methods: This multicentre, randomized, double-blind, double-dummy, active-controlled study was conducted in China from 2022 to 2024. Patients aged 18–75 years who met the 2015 ACR preliminary criteria for the classification of acute arthritis of primary gout (GA), were contraindicated, intolerant, or unresponsive to NSAIDs and/or colchicine, and experienced ≥2 episodes in the previous 12 months were screened for eligibility. Eligible patients were stratified by baseline visual analog scale (VAS) pain score of the target joint (50 mm ≤ VAS < 70 mm, and 70 mm ≤ VAS ≤ 100 mm) and randomized in a 1:1 ratio to receive either a single subcutaneous dose of Firsekibart (200 mg) or an intramuscular dose of Compound Betamethasone (CB) (7 mg). The study consisted of a 24-week double-blind core treatment period followed by a 24-week open-label extension. The core studies had two co-primary efficacy endpoints: the change in pain intensity from baseline to 72 hours in the most affected joint measured by VAS (0–100mm) with non-inferiority testing and the time to first new episode over 12-week with superiority testing. All efficacy endpoints were analyzed with the full analysis set (FAS) (i.e. all randomized patients who received study drugs had at least one post-baseline efficacy assessment), and safety assessments were based on the safety analysis set (SS) (i.e. all randomized patients who received study drugs and had at least one post-baseline safety assessment). Results: A total of 313 patients were randomized, one patient in the Firsekibart group did not receive the study drug, and another in the CB group lacked valid efficacy data, with final 311 included in the FAS analysis. The median age was 42, 98.7% were men. The duration of GA was 103.89 months, and 89.4% patients had more than 3 episodes in the preceding 12 months. Compared with CB, Firsekibart showed a non-inferiority effect on the reduction in pain intensity from baseline to 72 hours (-57.09 mm [95% CI: -60.08, -54.10] vs. -53.77 mm [95% CI: -56.77, -50.77]) (Least Squares Mean). Firsekibart significantly delayed the time to the first new flare (not estimable vs. 45 days) and reduced the risk of a new flare over the 12-week period by 90% (HR: 0.10; 95% CI: 0.06, 0.17; p＜0.0001) and over the 24-week period by 87% (HR: 0.13; 95% CI: 0.08, 0.21; p＜0.0001). Time to first achieving 50% pain reduction in the target joint was similar (24.5 h [95% CI: 24.10, 48.00] vs. 24.3 h [95% CI: 24.03, 48.00]) (median). A significantly lower proportion of patients treated with Firsekibart experienced at least one new flare over 12 weeks (10.9% vs. 65.2%) and 24 weeks (14.7% vs. 66.5%) compared to those treated with CB. Consistently, the mean number of new flares per patient was significantly lower in the Firsekibart group compared to the CB group over both 12 weeks (0.2 ± 0.52 vs. 1.2 ± 1.27) and 24 weeks (0.2 ± 0.79 vs. 1.6 ± 1.79) (mean ± SD). The total adverse events and treatment-related adverse events were 365 and 146 in the Firsekibart-treated group, versus 471 and 188 in the CB-treated group, respectively. Treatment-related serious adverse events were reported in 3 patients and all in CB-treated group. Conclusion: Compared with CB, Firsekibart demonstrated non-inferior short-term pain relief while offering significantly better prevention of new flares and an improved safety profile in patients with acute gouty arthritis. REFERENCES: NIL . Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.