title: Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The objective of this study was to provide a detailed account of IRs with pegloticase therapy.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Herbert S B
authors.initials: HS
authors.lastname: Baraf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yood
authors.forename: Faith D
authors.initials: FD
authors.lastname: Ottery
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.forename: Michael A
authors.initials: MA
authors.lastname: Becker
mesh_terms: D000368:Aged; D002908:Chronic Disease; D017326:Clinical Trials, Phase III as Topic; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006073:Gout / Q000097:blood* / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014503:Urate Oxidase / Q000009:adverse effects*; D014527:Uric Acid / Q000097:blood
chemical_list: D006074:Gout Suppressants; D014527:Uric Acid; D011092:Polyethylene Glycols; D014503:Urate Oxidase; C031545:Pegloticase