title: Urate-lowering therapy for the management of gout: a summary of 2 Cochrane reviews.
abstract: OBJECTIVE
  To systematically review the evidence on the efficacy, safety, and cost-effectiveness of urate-lowering therapy for gout: xanthine oxidase inhibitors (allopurinol and febuxostat), uricosuric medications (benzbromarone, probenecid and sulfinpyrazone), and uricases (pegloticase and rasburicase).
  
  
  METHODS
  A systematic review was performed as part of the 3e (Evidence, Expertise, Exchange) Initiative on Gout. The primary efficacy outcomes were frequency of acute gout attacks, study participant withdrawal due to adverse events, and cost-effectiveness. Serum urate-lowering was a secondary outcome and was the most commonly reported outcome in the included trials.
  
  
  RESULTS
  The search identified 17 articles for efficacy, 31 for safety, and 3 for cost-effectiveness. The main outcome described in these studies was serum urate-lowering. Allopurinol, febuxostat, and pegloticase are all effective at lowering serum urate compared to placebo and febuxostat (≥ 80 mg) was more effective at lowering serum urate than allopurinol. Compared to probenecid, benzbromarone was more effective at lowering serum urate. Regarding acute gout attacks, pegloticase and febuxostat (≥ 120 mg) resulted in more acute attacks than placebo. Regarding the primary safety outcome, more withdrawals due to adverse events were seen only when pegloticase was compared to placebo. The two trials of cost-effectiveness were inconclusive.
  
  
  CONCLUSIONS
  There is currently moderate quality data supporting the efficacy and safety of allopurinol, febuxostat, benzbromarone, and probenecid in gout. Pegloticase, while efficacious, is associated with more withdrawals due to adverse events and infusion reactions. There is insufficient evidence currently with respect to the cost-effectiveness or the most optimal sequencing of urate-lowering therapy.
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Alison S
authors.initials: AS
authors.lastname: Kydd
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Rakhi
authors.initials: R
authors.lastname: Seth
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Rachelle
authors.initials: R
authors.lastname: Buchbinder
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Louise
authors.initials: L
authors.lastname: Falzon
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Edwards
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Désirée M
authors.initials: DM
authors.lastname: van der Heijde
authors.affiliation: From the Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada; Department of Rheumatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Monash Department of Clinical Epidemiology, Cabrini Hospital; and Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Malvern, Victoria, Australia; Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, NY, USA; Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands; Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto General Research Institute, University Health Network; Institute for Work and Health, Mount Sinai Hospital, Toronto, Ontario, Canada.A.S. Kydd, MD, PhD, FRCPC, Clinical Assistant Professor, Division of Rheumatology, University of British Columbia; R. Seth, BM, MRCP, Department of Rheumatology, University Hospital Southampton NHS Foundation Trust; R. Buchbinder, MBBS (Hons), MSc, PhD, FRACP, Director, Monash Department of Clinical Epidemiology, Cabrini Hospital; and Professor, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; L. Falzon, PGDipInf, Center for Behavioral Cardiovascular Health, Columbia University Medical Center; C.J. Edwards, MBBS, MD, FRCP, Department of Rheumatology and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust; D.M. van der Heijde, MD, PhD, Professor of Rheumatology, Rheumatology Department, Leiden University Medical Center; C. Bombardier, MD, FRCPC, Professor, Division of Rheumatology and Institute of Health Policy, Management, and Evaluation, University of Toronto; and Toronto Ge
authors.forename: Claire
authors.initials: C
authors.lastname: Bombardier
mesh_terms: D006073:Gout / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*; D014528:Uricosuric Agents / Q000627:therapeutic use*
chemical_list: D014528:Uricosuric Agents; D014527:Uric Acid
keywords: ALLOPURINOL; FEBUXOSTAT; GOUT; PEGLOTICASE; TREATMENT; URICOSURIC AGENTS