Background/Purpose: Approximately 70% of adults with gout have CKD (Chronic Kidney Disease) ≥stage 3 (i.e estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2), significantly restricts treatment options such as colchicine or NSAIDs due to the potential renal toxicity. Firsekibart, previously known as Genakumab, is a novel IgG4/λ anti-human-IL-1β monoclonal antibody eliminated by degradation through intracellular enzymes rather than excretion through the kidney，making it a significant option for gout with CKD. Here, we report the efficacy and safety of Firsekibart vs compound betamethasone(CB) in a subgroup of patients with eGFR < 60ml/min/1.73m2.

Methods: This multicenter, randomized, double-blind, double-dummy, active-controlled phase III clinical trial was conducted across 51 centers in China. ( NCT05983445). Patients (aged 18-75) who had acute arthritis of primary gout (GA) and contraindicated of, intolerance of, or unresponsiveness to NSAIDs and/or colchicine, with ≥2 episodes during the previous 12 months were screened for eligibility. Patients were randomized in a 1:1 ratio to either a single subcutaneous dose of Firsekibart (200 mg) or an intramuscular dose of CB 7 mg treatment. The co-primary endpoints were change in pain intensity from baseline to 72 hours in the most affected joint measured on VAS (0–100 mm) with non-inferiority testing and the time to first new episode over 12 weeks with superiority testing. Secondary endpoints included percentage of patients with at least one new flare (12weeks, 24weeks) and the safety evaluation.

Results: Of 313 patients, 42 patients had eGFR< 60ml/min/1.73m2 at baseline (21 in Firsekibart group and 21 in CB group). 95.24%patients had more than 3 episodes in the preceding 12 months and 50% patients had gouty tophi. Firsekibart demonstrated a competing effect in reducing VAS pain score (58.22 (-67.516, -48.927) mm vs. -58.33 (-67.635, -49.022) mm) (Least Squares Mean(95CI%)). Compared to CB, Firsekibart significantly delayed median time to first new episode (Not estimable vs 21 days) ，reduced the risk of a new flare by 98% over the 12-week period (HR 0.02; p=0.0002), by 96% over the 24-week period (HR 0.04, p＜0.0001). A significantly lower proportion of patients treated with Firsekibart experienced at least one new flare over 12 weeks (4.76% vs. 95.24%) and 24 weeks (9.52% vs. 95.00%).The treatment emergent adverse events and treatment-related adverse events were 10 (47.6%) and 7 (33.3%) in the Firsekibart-treated group, versus 11 (52.4%) and 6 (28.6%) in the CB-treated group. No serious adverse events were reported in Firsekibart-treated group. Besides, neitiher Firsekibart nor CB showed significant damage to kidney function, only one patient in Firsekibart-treated group experienced renal function deterioration over 24 weeks after treatment. (eGFR decreased from 30~60 to < 30ml/min/1.73m2).

Conclusion: Compared with a potent long-acting corticosteroid (Compound betamethasone), Firsekibart showed a comparable effect in pain relief and offering significantly better prevention of new flares in GA patients with eGFR < 60ml/min/1.73m2. The safety profile in this sub population was consistent with that of the overall study population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-firsekibart-in-acute-gouty-arthritis-patients-with-egfr-60ml-min-1-73m2a-post-hoc-analysis-of-24-week-data/