Research Summary

Shorter-Duration Pegloticase Infusions Safe and Effective in Uncontrolled Gout

Miranda Manier, BA

Key Highlights

  • Pegloticase infused over 60 minutes was well tolerated, with infusion reactions in 6% of patients.
  • Anaphylaxis occurred in 1.7% of patients.
  • Two-thirds of patients achieved sustained urate lowering at 24 weeks.
  • Safety, tolerability, and efficacy outcomes were comparable to traditional 120-minute infusions.

The AGILE phase 4 trial evaluated whether pegloticase, an intravenous therapy indicated for patients with uncontrolled gout refractory to standard urate-lowering treatment, could be administered over shorter infusion times than the current 120-minute standard.

The study was designed to address logistical challenges associated with lengthy infusion durations while ensuring safety and efficacy were not compromised.

Patients with uncontrolled gout were sequentially enrolled into infusion cohorts of 60, 45, and 30 minutes, with all receiving oral methotrexate as co-therapy. Based on interim safety reviews, the 60-minute infusion duration was selected for full enrollment. Participants were followed for 24 weeks. The primary endpoint was the incidence of infusion reactions, including anaphylaxis. Secondary efficacy and safety endpoints included treatment response rate, discontinuations due to infusion reaction, anaphylaxis, or loss of serum urate–lowering response, and time to discontinuation.

A total of 116 patients were enrolled in the 60-minute infusion cohort. Infusion reactions occurred in 6.0% of patients (7 of 116), with anaphylaxis reported in 1.7% (2 of 116). The treatment response rate, defined as maintaining serum urate <6 mg/dL for at least 80% of the time during weeks 20–24, was achieved in 67.2% of patients (78 of 116). Pegloticase discontinuation due to infusion reaction, anaphylaxis, or loss of serum urate–lowering response occurred in 19.0% of patients (22 of 116).

Adverse events were common but generally manageable, occurring in 77.6% of patients (90 of 116). Serious adverse events were reported in 3.4% (4 of 116). The overall safety profile was consistent with prior experience, and the incidence of clinically significant infusion reactions was low.

As the investigators concluded, “Safety, tolerability, and efficacy results of pegloticase infused for 60 minutes were comparable to traditional infusion durations (120 minutes), making shorter infusion times feasible.”

Reference
Troum OM, Botson JK, Fang F, Mohammad AS, Verma S, LaMoreaux B. Safety, tolerability, and efficacy of shorter infusion durations of pegloticase administered to patients with uncontrolled gout receiving methotrexate: AGILE trial. J Clin Rheumatol. Published online September 23, 2025. doi:10.1097/RHU.0000000000002283