title: A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis.
abstract: OBJECTIVE
  Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA.
  
  
  METHODS
  In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28-CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24).
  
  
  RESULTS
  326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012-June 2013). Mavrilimumab treatment significantly reduced DAS28-CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: -1.90 (0.14), 100 mg: -1.64 (0.13), 30 mg: -1.37 (0.14), placebo: -0.68 (0.14); p<0.001; all dosages compared with placebo).Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p<0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified.
  
  
  CONCLUSIONS
  Mavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential.
  
  
  BACKGROUND
  NCT01706926; results.
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: Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Center for Rheumatology, Albany Medical College, Albany, New York, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Kremer
authors.affiliation: Universidad de Chile and Hospital San Juan de Dios, Santiago, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Miranda
authors.affiliation: Division of Rheumatology, Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Korkosz
authors.affiliation: Institute of Rheumatology, Charles University, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Vencovsky
authors.affiliation: Department of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.affiliation: Organizacion Medica de Investigación, Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mysler
authors.affiliation: MedImmune, Cambridge, UK.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sleeman
authors.affiliation: MedImmune, Cambridge, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Godwood
authors.affiliation: MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Sinibaldi
authors.affiliation: MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Xiang
authors.identifier: http://orcid.org/0000-0001-6441-5174
authors.initials: X
authors.lastname: Guo
authors.affiliation: MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Wendy I
authors.initials: WI
authors.lastname: White
authors.affiliation: MedImmune, Mountain View, California, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: MedImmune, Mountain View, California, USA.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Wu
authors.affiliation: MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ryan
authors.affiliation: MedImmune, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Close
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D019233:Retreatment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; C000621868:GM-CSF receptor-alpha subunit, human; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C561644:mavrilimumab; D002097:C-Reactive Protein; D008727:Methotrexate
keywords: Cytokines; Rheumatoid Arthritis; Treatment