title: Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis.
abstract: OBJECTIVE
  Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA).
  
  
  METHODS
  Subcutaneous mavrilimumab (10 mg, 30 mg, 50 mg, or 100 mg) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ≥1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12.
  
  
  RESULTS
  55.7% of mavrilimumab-treated subjects met the primary endpoint versus 34.7% placebo (p=0.003) at week 12; for the 10 mg, 30 mg, 50 mg, and 100 mg groups, responses were 41.0% (p=0.543), 61.0% (p=0.011), 53.8% (p=0.071), and 66.7% (p=0.001) respectively. Response rate differences from placebo were observed at week 2 and increased throughout the treatment period. The 100 mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 (23.1% vs 6.7%, p=0.016), all categories of the American College of Rheumatology (ACR) criteria (ACR20: 69.2% vs 40.0%, p=0.005; ACR50: 30.8% vs 12.0%, p=0.021; ACR70: 17.9% vs 4.0%, p=0.030), and the Health Assessment Questionnaire Disability Index (-0.48 vs -0.25, p=0.005). A biomarker-based disease activity score showed a dose-dependent decrease at week 12, indicating suppression of disease-related biological pathways. Adverse events were generally mild or moderate in intensity. No significant hypersensitivity reactions, serious or opportunistic infections, or changes in pulmonary parameters were observed.
  
  
  CONCLUSIONS
  Mavrilimumab induced rapid clinically significant responses in RA subjects, suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA.
authors.affiliation: Charité-University Medicine Berlin, Department of Rheumatology and Clinical Immunology Free University and Humboldt University, Berlin, Germany. Gerd.Burmester@charite.de
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Duncan
authors.initials: D
authors.lastname: Porter
authors.forename: Olga
authors.initials: O
authors.lastname: Barbarash
authors.forename: Mykola
authors.initials: M
authors.lastname: Vatutin
authors.forename: Istvan
authors.initials: I
authors.lastname: Szombati
authors.forename: Ehsanollah
authors.initials: E
authors.lastname: Esfandiari
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sleeman
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kane
authors.forename: Guy
authors.initials: G
authors.lastname: Cavet
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Alex
authors.initials: A
authors.lastname: Godwood
authors.forename: Fabio
authors.initials: F
authors.lastname: Magrini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D005938:Glucocorticoids; C561644:mavrilimumab; D008727:Methotrexate