title: Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.
abstract: BACKGROUND
  Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need.
  
  
  OBJECTIVE
  To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout.
  
  
  METHODS
  Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406.
  
  
  METHODS
  Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group).
  
  
  METHODS
  Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6.
  
  
  RESULTS
  In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008).
  
  
  CONCLUSIONS
  Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00325195.
authors.affiliation: Duke Clinical Research Unit, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.forename: Herbert S B
authors.initials: HS
authors.lastname: Baraf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yood
authors.forename: N Lawrence
authors.initials: NL
authors.lastname: Edwards
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Gutierrez-Urena
authors.forename: Edward L
authors.initials: EL
authors.lastname: Treadwell
authors.forename: Janitzia
authors.initials: J
authors.lastname: Vázquez-Mellado
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Zeb
authors.initials: Z
authors.lastname: Horowitz
authors.forename: William
authors.initials: W
authors.lastname: Huang
authors.forename: Allan N
authors.initials: AN
authors.lastname: Maroli
authors.forename: Royce W
authors.initials: RW
authors.lastname: Waltrip
authors.forename: Steven A
authors.initials: SA
authors.lastname: Hamburger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Becker
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use; D002908:Chronic Disease; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004800:Enzymes, Immobilized / Q000008:administration & dosage*; D005260:Female; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016896:Treatment Outcome; D014503:Urate Oxidase / Q000008:administration & dosage*; D014527:Uric Acid / Q000097:blood*
chemical_list: D004800:Enzymes, Immobilized; D006074:Gout Suppressants; D014527:Uric Acid; D011092:Polyethylene Glycols; D000493:Allopurinol; D014503:Urate Oxidase; C031545:Pegloticase