Safety, Tolerability, and Efficacy of Shorter Infusion Durations of Pegloticase Administered to Patients With Uncontrolled Gout Receiving Methotrexate: AGILE Trial.

Abstract

Background/objective: Pegloticase is indicated to lower serum urate (SU) in patients with uncontrolled gout refractory to urate-lowering therapy. Pegloticase is infused for 120 minutes every 2 weeks, which can create logistical barriers. The phase 4, open-label AGILE trial (NCT04511702) assessed the safety and efficacy of shorter-duration pegloticase infusions in patients with uncontrolled gout.

Methods: AGILE examined 60-, 45-, and 30-minute intravenous pegloticase infusion durations co-administered with oral methotrexate. The desirable infusion duration was determined by enrolling patients sequentially into initial cohorts and assessing them over 24 weeks. The primary endpoint was infusion reaction (IR) incidence, including anaphylaxis. Key efficacy/safety endpoints included treatment response rate; pegloticase discontinuation due to IR; anaphylaxis, or SU-lowering response loss; and time to IR that led to discontinuation, anaphylaxis, or SU-lowering response loss.

Results: The 60-minute infusion cohort (n=116) was chosen and enrolled based on safety reviews. Overall, 6.0% of patients (7/116; 95% CI: 2.5%-12.0%) experienced IRs, including anaphylaxis in 1.7% (2/116) of patients. A treatment response was observed in 67.2% (78/116; 95% CI: 57.9%-75.7%) of patients (SU <6 mg/dL for ≥80% of the time during weeks 20-24). Pegloticase discontinuation due to IR, anaphylaxis, or loss of SU-lowering response occurred in 19.0% (22/116; 95% CI: 12.3%-27.3%) of patients. At least 1 adverse event occurred in 77.6% (90/116) of patients; 3.4% (4/116) of patients had serious adverse events.

Conclusions: Safety, tolerability, and efficacy results of pegloticase infused for 60 minutes were comparable to traditional infusion durations (120 min), making shorter infusion times feasible.