Background/Purpose: Pegloticase, a recombinant modified mammalian uricase conjugated to mPEG, was approved for use in refractory chronic gout in the US in 2010. The Phase 3 clinical program comprised replicate, randomized, placebo-controlled trials (RCTs) followed by an open-label extension (OLE) study for a total treatment duration of up to 3 years. Here we focus on tophus resolution, flares, and tender/swollen joint counts with long-term pegloticase administration.

Methods: Patients entering the RCTs were >18 years of age, had baseline uric acid (UA) ≥8 mg/dL and at least one of the following: 3 or more self-reported gout flares during the prior 18 months, 1 or more tophi, or gouty arthropathy and contraindication to allopurinol or failure to normalize UA during 3 or more months of treatment at the maximum medically appropriate dose. The OLE enrolled patients at 46 centers in the US, Mexico and Canada who completed a RCT. Pegloticase dosing regimen (8 mg q2wks or q4wks) was determined at entry to the OLE and could be adjusted twice during the trial. All patients received prophylaxis for infusion reactions and flares. A tophus complete response was defined as 100% reduction in the measured area of at least 1 tophus of baseline diameter ≥5 mm without growth of any other baseline tophus or appearance of any new tophi. 547 evaluable tophi were present in 113 patients at baseline. Serial physician’s global assessments (GA) were scored on a visual analogue scale from 0 (very good) to 100 (very bad) as a measure of patient well-being resulting from disease activity and assessments of 54 joints for swelling or tenderness were also performed.

Results: Most subjects completing blinded treatment (151/157) entered the OLE study. Among the 149 patients treated with pegloticase in the OLE study (2 elected observation only), 110 had received pegloticase during randomized testing and 39 had received placebo. Mean UA was 10 mg/dL at the OLE baseline (see baseline definition below). After 1 year of OLE treatment (week 52 visit), 59% of patients remaining in the study (62/105) had UA levels below 6 mg/dL. Secondary endpoints over time are presented in the Table below at study baseline, Week 13 (first measurement), one year, and final visit.

Conclusion : Treatment with pegloticase for up to an additional 2.5 years beyond the 6 months of blinded trial participation was associated with ongoing benefits for patients. The OLE population data shown provides a conservative estimate of benefit as data are pooled for responders and non-responders. Patients undergoing sustained treatment with pegloticase can be expected to show meaningful clinical improvements with up to 3 years of therapy.