Monthly Pegloticase Dosing with Methotrexate Shows Promising Efficacy and Safety in Uncontrolled Gout
A Phase 4 study published in Annals of the Rheumatic Diseases evaluating monthly intravenous (Q4W) pegloticase infusions coadministered with methotrexate (MTX) has demonstrated promising results in patients with uncontrolled gout, supporting a simplified dosing strategy that could improve adherence and infusion efficiency.
The FORWARD I study assessed both 16 mg and 30 mg doses given monthly for up to 12 months among 51 bionaïve patients with uncontrolled gout, randomized into 2 cohorts—25 received 16 mg and 26 received 30 mg of pegloticase. All patients underwent a 4-week MTX run-in (15 mg/week with folic acid), followed by pegloticase infusions every 4 weeks for 24 weeks, with an optional extension to 48 weeks.
By Month 6, serum uric acid (sUA)–lowering response, defined as maintaining sUA <6 mg/dL for at least 80% of the time, was achieved in 68.0% of the 16-mg group and 73.1% of the 30-mg group, the study reported. Sustained response continued into the extension period. At Month 12, 88.2% of patients in the 16-mg cohort and 68.4% in the 30-mg cohort remained responders. The median proportion of time patients maintained sUA <6 mg/dL was 100% across both dosing groups for both 24- and 48-week periods.
Infusion reactions (IR), including anaphylaxis, occurred in 16.0% of patients in the 16-mg group and 11.5% in the 30-mg group. No IRs occurred after Week 24. “If the discontinuation criteria had been properly applied, the IR rate would be ~8% in both groups,” the authors noted. Reported cardiac adverse events were reviewed and determined not to meet criteria for major adverse cardiac events (MACE).
“These data demonstrate the feasibility of Q4W increased-dose pegloticase while maintaining safety and efficacy comparable to pegloticase 8 mg Q2W in MIRROR RCT,” the authors concluded. Pharmacokinetic analysis is ongoing to inform dose selection for the upcoming Phase 3 confirmatory trial.
These findings suggest that monthly dosing of pegloticase with MTX may offer a more patient-friendly regimen without compromising therapeutic outcomes, particularly for those with uncontrolled gout requiring long-term urate-lowering therapy.
Reference
Troum O, Botson J, Fang F, et al. Safety and efficacy of monthly dosing of pegloticase (every 4 weeks) with methotrexate co-administration in patients with uncontrolled gout: phase 4 forward open-label trial. Annals of the Rheumatic Diseases. 2025;84:1225-1226. doi:10.1016/j.ard.2025.06.503
