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:
CreatorsEmailORCIDORCID Put Code
Burmester, Gerd R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McInnes, Iain B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kremer, JoelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miranda, PedroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korkosz, MariuszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vencovsky, JiriUNSPECIFIEDorcid.org/0000-0002-0851-0713UNSPECIFIED
Rubbert-Roth, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mysler, EduardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sleeman, Matthew A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Godwood, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sinibaldi, DominicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guo, XiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
White, Wendy I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, BingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Chi-YuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ryan, Patricia C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Close, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weinblatt, Michael E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
COLONY-STIMULATING FACTOR; DOUBLE-BLIND; DISEASE; SAFETY; IMMUNOGENICITY; VALIDATION; EFFICACY; CRITERIA; DAMAGEMultiple languages
RheumatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23028

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