Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis

• Published in: Annals of the rheumatic diseases Vol. 72; no. 9; pp. 1445 - 1452
• Main Authors: Burmester, Gerd R, Weinblatt, Michael E, McInnes, Iain B, Porter, Duncan, Barbarash, Olga, Vatutin, Mykola, Szombati, Istvan, Esfandiari, Ehsanollah, Sleeman, Matthew A, Kane, Christopher D, Cavet, Guy, Wang, Bing, Godwood, Alex, Magrini, Fabio
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.09.2013; Elsevier Limited; BMJ Publishing Group
• Series: Extended report
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - physiopathology; Biomarkers; Clinical and Epidemiological Research; Disability Evaluation; Disease Activity; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids - therapeutic use; Health Status; Humans; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lung diseases; Male; Methotrexate - therapeutic use; Middle Aged; Rheumatoid Arthritis; Severity of Illness Index; Studies; Surfactants; Treatment; Treatment Outcome; Young Adult; Rheumatoid Arthritis; Disease Activity; Treatment
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2012-202450

Objectives 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.