Universität zu Köln

Burmester, Gerd R., McInnes, Iain B., Kremer, Joel, Miranda, Pedro, Korkosz, Mariusz, Vencovsky, Jiri ORCID: 0000-0002-0851-0713, Rubbert-Roth, Andrea, Mysler, Eduardo, Sleeman, Matthew A., Godwood, Alex, Sinibaldi, Dominic, Guo, Xiang, White, Wendy I., Wang, Bing, Wu, Chi-Yuan, Ryan, Patricia C., Close, David and Weinblatt, Michael E. (2017). A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann. Rheum. Dis., 76 (6). S. 1020 - 1031. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

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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-a, 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Burmester, Gerd R. UNSPECIFIED UNSPECIFIED UNSPECIFIED McInnes, Iain B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kremer, Joel UNSPECIFIED UNSPECIFIED UNSPECIFIED Miranda, Pedro UNSPECIFIED UNSPECIFIED UNSPECIFIED Korkosz, Mariusz UNSPECIFIED UNSPECIFIED UNSPECIFIED Vencovsky, Jiri UNSPECIFIED orcid.org/0000-0002-0851-0713 UNSPECIFIED Rubbert-Roth, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Mysler, Eduardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Sleeman, Matthew A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Godwood, Alex UNSPECIFIED UNSPECIFIED UNSPECIFIED Sinibaldi, Dominic UNSPECIFIED UNSPECIFIED UNSPECIFIED Guo, Xiang UNSPECIFIED UNSPECIFIED UNSPECIFIED White, Wendy I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Bing UNSPECIFIED UNSPECIFIED UNSPECIFIED Wu, Chi-Yuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ryan, Patricia C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Close, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Weinblatt, Michael E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-230281
DOI:	10.1136/annrheumdis-2016-210624
Journal or Publication Title:	Ann. Rheum. Dis.
Volume:	76
Number:	6
Page Range:	S. 1020 - 1031
Date:	2017
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2060
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLONY-STIMULATING FACTOR; DOUBLE-BLIND; DISEASE; SAFETY; IMMUNOGENICITY; VALIDATION; EFFICACY; CRITERIA; DAMAGE Multiple languages Rheumatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23028