Monthly Pegloticase With MTX Appears Safe and Effective for Gout
Monthly dosing of pegloticase with methotrexate (MTX) coadministration appears both safe and effective for patients with uncontrolled gout, according to results from the open-label Phase 4 FORWARD I trial.
In this study, investigators explored whether a monthly infusion schedule—less burdensome than the biweekly standard—could maintain clinical benefits while potentially improving patient adherence and infusion logistics.
A total of 51 patients were enrolled across 2 cohorts: 25 participants received 16 mg and 26 received 30 mg of pegloticase every 4 weeks, in conjunction with oral MTX. Week 24 completion rates were 72.0% in the 16-mg cohort and 69.2% in the 30-mg cohort continuing treatment. In addition, 70.6% of participants chose to enter into a 24-week extension; 88.2% of the 16-mg group and 68.4% of the 30-mg group completed the full 48-week course.
At Month 6, 68.0% in the 16-mg group and 73.1% in the 30-mg group achieved the primary endpoint of maintaining serum uric acid (sUA) <6 mg/dL for ≥80% of the time. The time to loss of response (sUA ≥6 mg/dL) varied, with medians of 50.5 and 22.5 days, respectively. Patients in both cohorts maintained a median of 100% time with sUA <6 mg/dL through both Week 24 and Week 48.
The rate of infusion reactions (IRs), including anaphylaxis, was 16.0% for the 16-mg group and 11.5% for the 30-mg group during the full treatment period. However, consistent with findings from the MIRROR randomized controlled trial, no IRs were reported after Week 24. The authors commented, “[I]f the discontinuation criteria had been properly applied, the IR rate would be ~8% in both groups.” Potential major adverse cardiac events (MACE) occurred in 8.0% and 3.8% of patients; however, none were ultimately deemed MACE by the sponsor.
The results suggest a viable alternative to biweekly dosing, particularly for patients seeking a less intensive treatment regimen, the investigators stated, noting that “decreasing the frequency of pegloticase to a single monthly (Q4W) IV dose will further improve treatment logistics, pt adherence and infusion efficiency.”
Reference:
Troum O, Botson J, Fang F et al. Safety and efficacy of monthly dosing of pegloticase with methotrexate co-administration in patients with uncontrolled gout: phase 4 FORWARD open-label trial. Abstract POS1153. Presented at European Congress of Rheumatology. June 11-14, 2025. Barcelona, Spain.
