Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3).
Peter C Taylor, Michael E Weinblatt, Iain B McInnes, Tatsuya Atsumi, Vibeke Strand, Tsutomu Takeuchi, Marguerite Bracher, David Brooks, John Davies, Christopher Goode, Anubha Gupta, Sumanta Mukherjee, Ciara O'Shea, Didier Saurigny, Lorrie A Schifano, Celia Shelton, Julia E Smith, Millie Wang, Reena Wang, Sarah Watts, Roy M Fleischmann
Author Information
Peter C Taylor: Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK peter.taylor@kennedy.ox.ac.uk. ORCID
Michael E Weinblatt: Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Iain B McInnes: College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Tatsuya Atsumi: Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Vibeke Strand: Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA. ORCID
Tsutomu Takeuchi: Department of Internal Medicine, Division of Rheumatology, Keio University School of Medicine, Tokyo, Japan. ORCID
Marguerite Bracher: GSK, Stevenage, UK.
David Brooks: GSK, Collegeville, Pennsylvania, USA.
John Davies: GSK, Brentford, UK.
Christopher Goode: GSK, Brentford, UK.
Anubha Gupta: GSK, Stevenage, UK.
Sumanta Mukherjee: GSK, Collegeville, Pennsylvania, USA.
Ciara O'Shea: GSK, Dublin, Ireland.
Didier Saurigny: GSK, Stevenage, UK.
Lorrie A Schifano: GSK, Durham, North Carolina, USA.
Celia Shelton: GSK, Collegeville, Pennsylvania, USA.
Julia E Smith: GSK, Stevenage, UK.
Millie Wang: GSK, Brentford, UK.
Reena Wang: GSK, Collegeville, Pennsylvania, USA.
Sarah Watts: GSK, Stevenage, UK.
Roy M Fleischmann: Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. ORCID
OBJECTIVES: To investigate the efficacy and safety of otilimab, an anti-granulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis and an inadequate response to conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (DMARDs) and/or Janus kinase inhibitors. METHODS: ContRAst 3 was a 24-week, phase III, multicentre, randomised controlled trial. Patients received subcutaneous otilimab (90/150 mg once weekly), subcutaneous sarilumab (200 mg every 2 weeks) or placebo for 12 weeks, in addition to csDMARDs. Patients receiving placebo were switched to active interventions at week 12 and treatment continued to week 24. The primary end point was the proportion of patients achieving an American College of Rheumatology ≥20% response (ACR20) at week 12. RESULTS: Overall, 549 patients received treatment. At week 12, there was no significant difference in the proportion of ACR20 responders with otilimab 90 mg and 150 mg versus placebo (45% (p=0.2868) and 51% (p=0.0596) vs 38%, respectively). There were no significant differences in Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, pain Visual Analogue Scale or Functional Assessment of Chronic Illness Therapy-Fatigue scores with otilimab versus placebo at week 12. Sarilumab demonstrated superiority to otilimab in ACR20 response and secondary end points. The incidence of adverse or serious adverse events was similar across treatment groups. CONCLUSIONS: Otilimab demonstrated an acceptable safety profile but failed to achieve the primary end point of ACR20 and improve secondary end points versus placebo or demonstrate non-inferiority to sarilumab in this patient population. TRIAL REGISTRATION NUMBER: NCT04134728.
