title: Long-term safety of pegloticase in chronic gout refractory to conventional treatment.
abstract: OBJECTIVE
  To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout.
  
  
  METHODS
  This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy.
  
  
  RESULTS
  Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence.
  
  
  CONCLUSIONS
  The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.
authors.affiliation: Rheumatology Section, The University of Chicago, Chicago, IL 60611-1713, USA. mbecker@medicine.bsd.uchicago.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Becker
authors.forename: Herbert S B
authors.initials: HS
authors.lastname: Baraf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yood
authors.forename: Aileen
authors.initials: A
authors.lastname: Dillon
authors.forename: Janitzia
authors.initials: J
authors.lastname: Vázquez-Mellado
authors.forename: Faith D
authors.initials: FD
authors.lastname: Ottery
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D004351:Drug Resistance; D004800:Enzymes, Immobilized / Q000009:adverse effects*; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D011092:Polyethylene Glycols / Q000009:adverse effects*; D012008:Recurrence; D016896:Treatment Outcome; D014503:Urate Oxidase / Q000009:adverse effects*; D014527:Uric Acid / Q000097:blood
chemical_list: D004800:Enzymes, Immobilized; D006074:Gout Suppressants; D014527:Uric Acid; D011092:Polyethylene Glycols; D014503:Urate Oxidase; C031545:Pegloticase
keywords: Gout; Rheumatoid Arthritis; Treatment