title: Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy.
abstract: BACKGROUND
  Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.
  
  
  METHODS
  Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.
  
  
  RESULTS
  Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).
  
  
  CONCLUSIONS
  Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.
  
  
  BACKGROUND
  NCT00325195, NCT01356498.
authors.forename: Herbert S B
authors.initials: HS
authors.lastname: Baraf
authors.forename: Michael A
authors.initials: MA
authors.lastname: Becker
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: Vazquez-Mellado
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Rehrig
authors.forename: Faith D
authors.initials: FD
authors.lastname: Ottery
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yood
mesh_terms: D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use; D002908:Chronic Disease; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006073:Gout / Q000188:drug therapy* / Q000473:pathology; D006074:Gout Suppressants / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014503:Urate Oxidase / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood
chemical_list: D006074:Gout Suppressants; D014527:Uric Acid; D011092:Polyethylene Glycols; D000493:Allopurinol; D014503:Urate Oxidase; C031545:Pegloticase