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TOPLINE
Among patients with uncontrolled gout, monthly infusions of 16 mg or 30 mg pegloticase given with methotrexate maintained serum uric acid levels < 6 mg/dL in more than two thirds of patients through most of month 6; however, gout flares and infusion reactions occurred.
METHODOLOGY
- Researchers conducted a phase 4, open-label trial at multiple US centers to assess the efficacy and safety of monthly infusions of higher-dose pegloticase given with methotrexate in 51 adults with uncontrolled gout.
- The patients were first started on 15 mg weekly doses of oral methotrexate with folic acid for 4 weeks to assess their tolerance to methotrexate.
- Every 4 weeks, 25 patients (mean age, 54.2 years; 92.0% men) received 16 mg pegloticase via infusion, and 26 patients (mean age, 55.8 years; 96.2% men) received 30 mg pegloticase via infusion, with both groups continuing to receive methotrexate. Treatment lasted 24 weeks, with an option to extend to week 48.
- Researchers evaluated primary efficacy endpoints as the percentage of patients whose serum uric acid levels remained < 6 mg/dL for at least 80% of month 6 (responders) and the time until serum uric acid levels first rose back to ≥ 6 mg/dL.
- Secondary efficacy endpoints included drug levels, uric acid control over time, and the percentage of patients who developed antidrug antibodies. Safety was also assessed.
TAKEAWAY
- At month 6, 68.0% of the patients on 16 mg pegloticase and 73.1% on 30 mg pegloticase were responders; through week 24, uric acid rose back to 6 mg/dL or higher in eight patients per group after first dropping below that level. Among patients who continued into the extension, 88.2% on 16 mg and 68.4% on 30 mg pegloticase were responders at month 12.
- At week 16, median peak pegloticase concentrations were 9.0 µg/mL on 16 mg and 13.6 µg/mL on 30 mg pegloticase, measured in a small subset of patients. New or rising anti-polyethylene glycol antibodies appeared in 36.0% of patients on 16 mg and 46.2% on 30 mg pegloticase.
- Treatment-emergent adverse events occurred in 80.0% and 84.6% of the patients on 16 mg and 30 mg pegloticase, respectively, and most of these adverse events were mild to moderate.
- Infusion reactions (including anaphylaxis) occurred in 16.0% and 11.5% of the patients on 16 mg and 30 mg pegloticase, respectively. Gout flares occurred in 72.0% and 76.9% of the patients on 16 mg and 30 mg pegloticase, respectively, but did not lead to treatment discontinuation.
IN PRACTICE
"A monthly dosing regimen is anticipated to reduce the logistical treatment burden and healthcare utilization, but adherence, patient preference, and healthcare resource utilization were not formally evaluated in this study," the authors of the study wrote.
SOURCE
The study was led by Orrin M. Troum, MD, University of Southern California Keck School of Medicine, Los Angeles. It was published online on September 19 in Arthritis Research & Therapy.
LIMITATIONS
The findings may not be generalizable to patients outside of the US. Efficacy and safety of pegloticase given monthly as a monotherapy could not be assessed. Researchers did not evaluate the control of serum uric acid levels after discontinuation of the combination therapy.
DISCLOSURES
The study received funding from Amgen Inc., which also funded medical writing and editorial support. Four of the six authors reported being affiliated with Amgen Inc. Additional writing support was provided by an employee and stockholder of the funding company. The authors did not declare any competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
