In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported.
The objective of this study was to provide a detailed account of IRs with pegloticase therapy.
Data from 2 replicate, 6-month randomized trials and an open-label extension study were pooled. Infusions of pegloticase (8 mg) were administered biweekly or monthly; all patients received prophylaxis (antihistamine, acetaminophen, and corticosteroid) and were tested for urate levels prior to each infusion. An IR was defined by protocol as any otherwise unexplained adverse event or cluster of temporally related events occurring during or within 2 hours of infusion.
Infusion-related reactions occurred in 94 (45%) of 208 patients receiving pegloticase; 10 patients reported IRs at first infusion and 84 during subsequent infusions. Chest discomfort (15%), flushing (12%), and dyspnea (11%) were the most common symptoms. Most IRs were rated mild or moderate; 7% were rated severe. All IRs resolved with slowing, interrupting, or stopping the infusion. No patient required blood pressure or ventilatory support. Infusion-related reactions were associated with loss of pegloticase urate-lowering efficacy: 91% of all IRs occurred in patients with preinfusion serum uric acid concentrations (sUA) greater than 6 mg/dL. For patients sustaining preinfusion sUA of less than 6 mg/dL, IRs occurred in fewer than 1 per 100 infusions.
Phase 3 trial data combined with post hoc analyses demonstrated that knowledge of sUA preceding each pegloticase infusion and cessation of therapy when urate-lowering efficacy is lost provide a means to optimize the safety of pegloticase in clinical practice.
From the *Center for Rheumatology & Bone Research, Wheaton, MD; †Reliant Medical Group, Worcester, MA; ‡Savient Pharmaceuticals, Inc, Bridgewater, NJ; §Duke University Medical Center, Durham, NC; and ║The University of Chicago, Chicago, IL.
Development of this manuscript was supported by Savient Pharmaceuticals, Inc, and Crealta Pharmaceuticals LLC. Savient Pharmaceuticals, Inc, had licensed worldwide rights to the technology related to pegloticase from Duke University and Mountain View Pharmaceuticals. Those rights are now owned by Crealta Pharmaceuticals LLC.
H.S.B.B. previously received grant/research support from Savient Pharmaceuticals; currently receives grant/research support from Takeda, Regeneron, and Ardea Biosciences; and is a consultant for Takeda and Crealta. He is a member of the speakers’ bureau for Takeda and Savient. R.A.Y. received grant/research support from Savient Pharmaceuticals, Inc, and receives support from Takeda. F.D.O. was an employee of Savient Pharmaceuticals, Inc, at the time of manuscript development and submission. J.S.S. receives research/grant and/or consulting fees from Merck, Astra Zeneca, and Eli Lilly. He previously consulted for and received research/grant support from Savient Pharmaceuticals, Inc. He has an ownership position in Academic Partners for Medical Education LLC and holds nonremunerative positions of potential influence in the Medanta Duke Research Institute. M.A.B. receives grant/research support from Takeda and is/has been a paid consultant for Takeda, Ardea Biosciences (AstraZeneca), BioCryst, Regeneron, Crealta, CymaBay, Metabolex, and Sobi. He previously consulted for and received support from Savient Pharmaceuticals, Inc.
Correspondence: Herbert S. B. Baraf, MD, Center for Rheumatology & Bone Research, a Division of Arthritis and Rheumatism Associates, 2730 University Blvd West, Wheaton, MD 20902. E-mail: email@example.com.