OBJECTIVES: 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. TRIAL REGISTRATION NUMBER: NCT01706926; results.

Center for Rheumatology Albany Medical College Albany New York USA

Department of Internal Medicine University of Cologne Cologne Germany

Department of Rheumatology and Clinical Immunology Charité University Medicine Berlin Free University and Humboldt University Berlin Berlin Germany

Division of Rheumatology Department of Internal Medicine and Gerontology Jagiellonian University Medical College Krakow Poland

Division of Rheumatology Immunology and Allergy Brigham and Women's Hospital Boston Massachusetts USA

Institute of Infection Immunity and Inflammation University of Glasgow Glasgow UK

Institute of Rheumatology Charles University Prague Czech Republic

MedImmune Cambridge UK

MedImmune Gaithersburg Maryland USA

MedImmune Mountain View California USA

Organizacion Medica de Investigación Buenos Aires Argentina

Universidad de Chile and Hospital San Juan de Dios Santiago Chile

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Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor α Monoclonal Antibody: Long-Term Safety and Efficacy in Patients With Rheumatoid Arthritis

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ClinicalTrials.gov
NCT01706926