Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis.

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.

• Authors: Gerd R Burmester, Michael E Weinblatt, Iain B McInnes, Duncan Porter, Olga Barbarash, Mykola Vatutin, Istvan Szombati, Ehsanollah Esfandiari, Matthew A Sleeman, Christopher D Kane, Guy Cavet, Bing Wang, Alex Godwood, Fabio Magrini, EARTH Study Group
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 72 Issue 9 Pg. 1445-52 (Sep 01 2013) ISSN: 1468-2060 [Electronic] England
• PMID: 23234647 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Glucocorticoids
• mavrilimumab
• Methotrexate

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (adverse effects, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, immunology, physiopathology)
• Disability Evaluation
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glucocorticoids (therapeutic use)
• Health Status
• Humans
• Leukocytes, Mononuclear (drug effects, immunology)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Severity of Illness Index
• Treatment Outcome
• Young Adult