Background Pegloticase is a PEGylated recombinant uricase approved in the US for treating adult patients with chronic refractory gout. As a biologic medication, pegloticase is administered intravenously every 2 weeks. It is currently not known whether a gap in the standard biweekly regimen can be tolerated or would be associated with a loss of efficacy. During the pivotal trial testing of pegloticase, some patients experienced a delay between participation in the randomized controlled trial (RCT) and the open-label extension (OLE) that followed. Analysis of the clinical impact of this gap was carried out to understand whether therapeutic benefit would be affected.
Objectives The objective of this analysis was to determine, among pegloticase responders, the effect of a 28 or more day gap between doses of pegloticase on the subsequent urate lowering response and frequency of infusion reactions.
Methods These analyses utilized results from two RCTs of pegloticase and a 2-year OLE. In the RCTs, 36 of 85 patients, who were dosed with pegloticase every two weeks, were classified as responders (persistent urate lowering during intensive monitoring at 3 and 6 months of the RCT), and went on to enroll in the OLE and receive additional doses of pegloticase. Of these 36 patients, 14 had a gap between pegloticase doses of more than 28 days.
Results Among the 14 patients with a gap of more than 28 days between doses of pegloticase therapy the length of the gap ranged from 34 to 167 days (mean =72.5 days, median =59.5 days). Of these 14 patients, 8 received pegloticase on an every-4-week dosing schedule in the OLE and 6 remained on every-2-week dosing. Ten of the 14 patients maintained their serum urate level <6mg/dL in the OLE. Five of 6 that remained on every 2 week dosing and 5 of 8 that went to every 4 week dosing continued to have serum urate <6mg/dL. (see table 1). By logistic regression analysis, the length of the gap had no significant effect on the subsequent urate lowering effect of pegloticase. Of the fourteen patients with a gap in pegloticase therapy, 2 (14%) had infusion reactions during a total of 632 infusions in the OLE yielding a re-treatment IR rate of 0.32%.
Conclusions The majority of patients in this limited dataset who were previously responders to pegloticase dosed every 2 weeks continued to maintain a serum urate lowering response to pegloticase after a gap in therapy. Infusion reactions during re-treatment occurred in 2 patients with a re-treatment infusion reaction rate of 0.32%.
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Disclosure of Interest H. Baraf Consultant for: Horizon Pharma, Takeda, Ironwood, A. Morton Consultant for: Pfizer, Sanofi Regeneron, Ironwood, Horizon, Speakers bureau: Prizer, Amgen, Abbvie, Janssen, Celgene, Horizon, Novartis, Ironwood, B. LaMoreaux Employee of: Horizon Pharma, J. Kent Employee of: Horizon Pharma