title: Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial.
abstract: OBJECTIVE
  To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA).
  
  
  METHODS
  In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed.
  
  
  RESULTS
  The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors.
  
  
  CONCLUSIONS
  Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Fleischmann
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, Texas, USA.
authors.forename: Martine
authors.initials: M
authors.lastname: Jasson
authors.affiliation: Department of Research and Development, Sanofi, Paris, France.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Radin
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: Stefano
authors.initials: S
authors.lastname: Fiore
authors.affiliation: Department of Research and Development, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Research and Development, Sanofi, Bridgewater, New Jersey, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
authors.affiliation: Department of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D019947:Receptors, Interleukin-6; D002097:C-Reactive Protein; C000592401:sarilumab; D008727:Methotrexate
keywords: Cytokines; DMARDs (biologic); Rheumatoid Arthritis; Treatment