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A randomised phase IIb study of mavrilimumab, a novel GM–CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis

2017; BMJ; Volume: 76; Issue: 6 Linguagem: Inglês

10.1136/annrheumdis-2016-210624

1468-2060

Gerd R Burmester, Iain B. McInnes, Joel M. Kremer, Pedro C. Miranda, Mariusz Korkosz, Jiří Vencovský, Andrea Rubbert‐Roth, Eduardo Mysler, Matthew A. Sleeman, A. Godwood, Dominic Sinibaldi, Xiang Guo, Wendy I. White, Bing Wang, Chi‐Yuan Wu, Patricia C. Ryan, David Close, Michael E. Weinblatt,

Immunotherapy and Immune Responses

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.