title: Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT).
  
  
  METHODS
  This phase III study was conducted in the United States, South Africa, Europe, and Asia. Adults (n = 1315, 18-80 yrs) with gout, who were initiating or continuing ULT, were randomized to treatment with weekly subcutaneous injections of rilonacept 160 mg or placebo for 16 weeks followed by a 4-week safety followup. The primary endpoint was safety, assessed by adverse events (AE) and laboratory values. Efficacy was a secondary endpoint.
  
  
  RESULTS
  Demographic and clinical characteristics were similar between treatments; predominantly male (87.8%), mean age 52.7 ± 11.3 years. Patients with ≥ 1 AE were 66.6% with rilonacept versus 59.1% placebo, with slightly more AE-related withdrawals with rilonacept (4.7% vs 3.0%) because of the greater incidence of injection site reactions (15.2% rilonacept, 3.3% placebo). Serious AE were similar in both groups, as were serious infections (0.9% placebo, 0.5% rilonacept); no tuberculosis or opportunistic infections occurred. Most common AE were headache, arthralgia, injection site erythema, accidental overdose, and pain in extremity. Of the 6 deaths, only 1 in the placebo group was considered treatment-related. At Week 16, rilonacept resulted in 70.3% fewer gout flares per patient (p < 0.0001), fewer patients with ≥ 1 and ≥ 2 gout flares (p < 0.0001), and 64.9% fewer gout flare days (p < 0.0001) relative to placebo.
  
  
  CONCLUSIONS
  Weekly subcutaneous administration of rilonacept 160 mg showed no new safety signals. The safety profile was consistent with previous studies. Rilonacept also significantly reduced the risk of gout flares. Clinicaltrials.gov identifier NCT00856206; EudraCT No. 2008-007784-16.
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc. john.sundy@duke.edu.
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.
authors.forename: Alan
authors.initials: A
authors.lastname: Kivitz
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Weinstein
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.
authors.forename: Richard
authors.initials: R
authors.lastname: Wu
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.
authors.forename: Shirletta
authors.initials: S
authors.lastname: King-Davis
authors.affiliation: From the Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Rheumatology, VA Medical Center and University of Pennsylvania, Philadelphia; Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania; Department of Clinical Sciences Immunology and Inflammation, Department of Biostatistics, and the Department of Clinical Operations, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.J.S. Sundy, MD, PhD, Department of Medicine, Duke University Medical Center; H.R. Schumacher, MD, Department of Rheumatology, VA Medical Center and University of Pennsylvania; A. Kivitz, MD, Department of Rheumatology, Altoona Center for Clinical Research; S.P. Weinstein, MD, PhD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.; R. Wu, PhD, Department of Biostatistics, Regeneron Pharmaceuticals Inc.; S. King-Davis, RN, MS, Department of Clinical Operations, Regeneron Pharmaceuticals Inc.; R.R. Evans, PharmD, Department of Clinical Sciences Immunology and Inflammation, Regeneron Pharmaceuticals Inc.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D038622:Internationality; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D006074:Gout Suppressants; D011993:Recombinant Fusion Proteins; D014527:Uric Acid; C531377:rilonacept
keywords: ALLOPURINOL; BIOLOGICAL THERAPY; GOUT; GOUTY ARTHRITIS; INTERLEUKINS