Phase 4 Studies Support Alternative Pegloticase Dosing Regimens for Uncontrolled Gout, with Orrin Troum, MD

New phase 4 studies of pegloticase support the feasibility of shorter infusions and higher-dose, less frequent infusions of the pegloticase + methotrexate (MTX) coadministration for people with uncontrolled gout.1,2

These findings are from the AGILE and FORWARD studies and were presented at June’s European Alliance of Associations for Rheumatology (EULAR) Congress 2025 held in Barcelona, Spain. The studies evaluated shorter, 60-minute infusions and high-dose monthly infusions, respectively.

Overall, the studies found that the investigational infusion regimens yielded comparable safety and efficacy as pegloticase 8 mg Q2W +MTX demonstrated in the pivotal MIRROR randomized control trial which led to the combination’s expanded approval in 2022.3 In each trial, achievement rates of the Month 6 sUA-lowering response primary endpoint were similar to that MIRROR trial. Furthermore, discontinuation rates, infusion reaction rates, and other adverse reaction rates were similar between the 2 trials and the MIRROR trial.1,2 Overall the studies support the feasibility of alternative dosing schemes that may ease patients’ treatment burden.

HCPLive spoke with Orrin Troum, MD, clinical professor of medicine, Keck School of Medicine, University of Southern California, and director, clinical rheumatology research, Providence St John's Hospital, Santa Monica, California, who served as a principal investigator AGILE and FORWARD, to learn more about how these latest investigations of pegloticase add to its clinical profile for treating uncontrolled gout.

HCPLive: How do these latest readouts from AGILE and FORWARD on monthly and shorter infusions of pegloticase add to our knowledge of its clinical benefits on uncontrolled gout?

Troum: Recent EULAR data from the FORWARD and AGILE trials demonstrated the safety and efficacy of new dosing regimens for Krystexxa (pegloticase) with Methotrexate(MTX) in uncontrolled gout patients, showcasing treatment efficacy and dosing frequency.

AGILE: evaluated a shorter infusion duration (60 minutes) of Krystexxa with coadministration of MTX and revealed a consistent efficacy and safety profile, as the standard 120-minute infusion protocol demonstrated in the MIRROR randomized controlled trial (RCT).

A SU-lowering response rate was achieved in 67.2% of uncontrolled gout patients at 6 months.

Between 82-88% of patients achieved target SU levels post Day 1 through Week 24.

FORWARD: demonstrated that monthly dosing of Krystexxa (16mg and 30 mg) with MTX every 4 weeks maintained a similar safety and efficacy profile to the standard 8 mg Q2W regimen found in the MIRROR RCT.

A SU-lowering response rate was achieved in 68-73% of uncontrolled gout patients at 6 months, with similar efficacy maintained at 12 months.

Median time patients sustained target SU levels was 100% from Day 1 to Week 24 or from Day 1 to Week 48 for both dosage cohorts.

HCPLive: What factors would guide shared decision-making for treatment regimens for people with uncontrolled gout?

Troum: Findings from the FORWARD and AGILE trials give the clinician and patient more flexibility in making a decision for the appropriate treatment regimen in patients with uncontrolled gout without compromising efficacy or safety.

HCPLive: What further research would you like to see done with pegloticase?

Troum: As the body of evidence supporting Krystexxa's efficacy, safety profile and real-world data continues to grow, as demonstrated by the findings of these two studies, other information regarding the effect of less corticosteroid use (Q 4 Week dosing instead of Q 2 week), and potentially using IL-1 blockers may be very useful in limiting corticosteroid use and worthy of future research.

This transcript has been edited for clarity.

REFERENCES

1. Troum O, Botson J, Fang F, Obermeyer K, Verma S, LaMoreaux B. ABS0756 Shorter Infusion Duration of Pegloticase Coadministered With Methotrexate in Patients with Uncontrolled Gout: Secondary and Exploratory Endpoints of the Agile Trial. Ann Rheum Dis. 2025;84:1587-1588. doi: 10.1016/j.ard.2025.06.974

2. Troum O, Botson J, Fang F, et al. POS1153 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. Ann Rheum Dis. 2025;84:1225-1226. doi: 10.1016/j.ard.2025.06.503

3. ‌Pine L. FDA Approves Pegloticase Injection Plus Methotrexate for Patients with Uncontrolled Gout. HCPLive. July 8, 2022. https://www.hcplive.com/view/fda-approves-pegloticase-injection-plus-methotrexate-for-patients-with-uncontrolled-gout