Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis

Burmester, G. R. et al. (2013) Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Annals of the Rheumatic Diseases, 72(9), pp. 1445-1452. (doi:10.1136/annrheumdis-2012-202450) (PMID:23234647) (PMCID:PMC3756523)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain
Authors: Burmester, G. R., Weinblatt, M. E., McInnes, I.B., Porter, D., Barbarash, O., Vatutin, M., Szombati, I., Esfandiari, E., Sleeman, M. A., Kane, C. D., Cavet, G., Wang, B., Godwood, A., and Magrini, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Annals of the Rheumatic Diseases
Publisher:B M J Group
ISSN:0003-4967
ISSN (Online):1468-2060
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in Annals of the Rheumatic Diseases 72(9):1445-1452
Publisher Policy:Reproduced under a Creative Commons License

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