title: Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial.
abstract: OBJECTIVE
  To compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.
  
  
  METHODS
  MONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.
  
  
  RESULTS
  Sarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (-3.28 vs -2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.
  
  
  CONCLUSIONS
  Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.
  
  
  BACKGROUND
  NCT02332590.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany.
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Sanofi Genzyme, Bridgewater, New Jersey, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Sanofi Genzyme, Bridgewater, New Jersey, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Patel
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: van Adelsberg
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Mangan
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.
authors.forename: Neil M H
authors.initials: NM
authors.lastname: Graham
authors.affiliation: Sanofi Genzyme, Bridgewater, New Jersey, USA.
authors.forename: Hubert
authors.initials: H
authors.lastname: van Hoogstraten
authors.affiliation: Sanofi Genzyme, Bridgewater, New Jersey, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bauer
authors.affiliation: Quantum Research, Puerto Varas, Chile.
authors.forename: Juan
authors.initials: J
authors.lastname: Ignacio Vargas
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000139:chemically induced; D007267:Injections / Q000009:adverse effects; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D019233:Retreatment; D012720:Severity of Illness Index
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; C000592401:sarilumab; D008727:Methotrexate
keywords: DMARDs (biologic); Rheumatoid Arthritis; Treatment