A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis
- PMID: 28213566
- DOI: 10.1136/annrheumdis-2016-210624
A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis
Abstract
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.
Keywords: Cytokines; Rheumatoid Arthritis; Treatment.
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Conflict of interest statement
Competing interests: GRB is a consultant and has received lecture fees from Abbvie, Bristol-Myers Squibb, MSD, Pfizer, Roche, UCB; IM has received grants and personal fees from Abbvie, AstraZeneca, Bristol-Myers Squibb, Janssen, MedImmune, MSD, Pfizer, UCB; JK is a shareholder and employee of Corrona; has received grants from Abbvie, Amgen, Genentech, Lilly, Pfizer; and is a consultant for Abbvie, Amgen Genentech, Lilly, Pfizer, BMS and MedImmune; PM has received grants from MedImmune; JV is a consultant for Biotest and Samsung Bioepics and has participated in speaker bureaus for Abbvie, MSD, Pfizer, UCB, Roche; AR-R received honoraria for consultation and lectures from Abbvie, Amgen, Chugai, Roche, UCB, MSD, Pfizer, Lilly, Sanofi, Novartis, BMS; EM has received a grant from Organizicion medica de Investigacion; MAS was formerly a full-time employee of MedImmune, a wholly owned subsidiary of AstraZeneca; AG, DS, XG, WIW, BW, C-YW, PCR and DC are employees of MedImmune and hold AstraZeneca shares; MEW has received research grants from Bristol-Myers Squibb, Crescendo Bioscience and UCB, and is a consultant for Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Corrona, Crescendo Bioscience, Genentech/Roche, Janssen, Lycera, Lilly, MedImmune, Merck, Pfizer, Regeneron, Sanofi, UCB.
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