title: An open-label, 6-month study of allopurinol safety in gout: The LASSO study.
abstract: OBJECTIVE
  Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses.
  
  
  METHODS
  Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA < 6.0mg/dL. The primary objective was evaluation of the safety of dose-titrated allopurinol by clinical and laboratory examinations at monthly visits. Secondary objectives included sUA-lowering efficacy and gout flare frequency.
  
  
  RESULTS
  Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was < 300 mg in 14.4%, 300 mg in 65.4%, and > 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the < 300-, 300-, and > 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA < 6.0mg/dL at month 6 was achieved by 35.9% of patients overall: 22.4%, 35.0%, and 48.3% in dosing categories < 300, 300, and > 300 mg, respectively.
  
  
  CONCLUSIONS
  This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.
authors.affiliation: Department of Medicine, University of Chicago Medicine, MC0930, 5841 S Maryland Ave, Chicago, IL 60637. Electronic address: mbecker@medicine.bsd.uchicago.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Becker
authors.affiliation: East-West Medical Research Institute, Honolulu, HI.
authors.forename: David
authors.initials: D
authors.lastname: Fitz-Patrick
authors.affiliation: Harvard Medical School, Boston, MA; Gout and Crystal Arthropathy Center, Massachusetts General Hospital, Boston, MA.
authors.forename: Hyon K
authors.initials: HK
authors.lastname: Choi
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: Clinical Research and Development, Ardea Biosciences Inc., San Diego, CA.
authors.forename: Chris
authors.initials: C
authors.lastname: Storgard
authors.affiliation: Medical Affairs, Ardea Biosciences, Inc., San Diego, CA, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Cravets
authors.affiliation: Biostatistics, Ardea Biosciences, Inc., San Diego, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Baumgartner
mesh_terms: D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000009:adverse effects* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003078:Colchicine / Q000627:therapeutic use; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006074:Gout Suppressants; D014527:Uric Acid; D000493:Allopurinol; D003078:Colchicine
keywords: Allopurinol; Dose titration; Gout; Hyperuricemia; Open-label study; Serum uric acid