Gerd R Burmester1, Iain B McInnes2, Joel Kremer3, Pedro Miranda4, Mariusz Korkosz5, Jiri Vencovsky6, Andrea Rubbert-Roth7, Eduardo Mysler8, Matthew A Sleeman9, Alex Godwood9, Dominic Sinibaldi10, Xiang Guo10, Wendy I White10, Bing Wang11, Chi-Yuan Wu11, Patricia C Ryan10, David Close9, Michael E Weinblatt12. 1. Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University, and Humboldt University Berlin, Berlin, Germany. 2. Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, UK. 3. Center for Rheumatology, Albany Medical College, Albany, New York, USA. 4. Universidad de Chile and Hospital San Juan de Dios, Santiago, Chile. 5. Division of Rheumatology, Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland. 6. Institute of Rheumatology, Charles University, Prague, Czech Republic. 7. Department of Internal Medicine, University of Cologne, Cologne, Germany. 8. Organizacion Medica de Investigación, Buenos Aires, Argentina. 9. MedImmune, Cambridge, UK. 10. MedImmune, Gaithersburg, Maryland, USA. 11. MedImmune, Mountain View, California, USA. 12. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
RCT Entities:
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Mary Canavan; Alice M Walsh; Vipul Bhargava; Sarah M Wade; Trudy McGarry; Viviana Marzaioli; Barry Moran; Monika Biniecka; Hannah Convery; Siobhan Wade; Carl Orr; Ronan Mullan; Jean M Fletcher; Sunil Nagpal; Douglas J Veale; Ursula Fearon Journal: JCI Insight Date: 2018-12-06
Authors: Andrew D Cook; Ming-Chin Lee; Reem Saleh; Hsu-Wei Khiew; Anne D Christensen; Adrian Achuthan; Andrew J Fleetwood; Derek C Lacey; Julia E Smith; Irmgard Förster; John A Hamilton Journal: JCI Insight Date: 2018-03-22
Authors: Frank R Brennan; Joy Cavagnaro; Kathleen McKeever; Patricia C Ryan; Melissa M Schutten; John Vahle; Gerhard F Weinbauer; Estelle Marrer-Berger; Lauren E Black Journal: MAbs Date: 2017-10-26 Impact factor: 5.857
Authors: Clint Piper; Vivian Zhou; Richard Komorowski; Aniko Szabo; Benjamin Vincent; Jonathan Serody; Maria-Luisa Alegre; Brian T Edelson; Reshma Taneja; William R Drobyski Journal: Blood Date: 2020-02-20 Impact factor: 22.113