Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X)
Objectives To investigate the long-term safety and efficacy of otilimab, an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody, for patients with rheumatoid arthritis (RA).Methods ContRAst X (NCT04333147) was a phase 3, multicentre, long-term extension trial. Patients with RA a...
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BMJ Publishing Group
2025-03-01
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| author | Tsutomu Takeuchi Iain B McInnes Peter C Taylor Roy M Fleischmann Vibeke Strand Michael E Weinblatt David Brooks Tatsuya Atsumi Paula Curtis Marguerite Bracher Anubha Gupta Didier Saurigny Celia Shelton Millie Wang Reena Wang Rina Nijhawan Ciara O'Shea Kirsty Rayner |
| author_facet | Tsutomu Takeuchi Iain B McInnes Peter C Taylor Roy M Fleischmann Vibeke Strand Michael E Weinblatt David Brooks Tatsuya Atsumi Paula Curtis Marguerite Bracher Anubha Gupta Didier Saurigny Celia Shelton Millie Wang Reena Wang Rina Nijhawan Ciara O'Shea Kirsty Rayner |
| author_sort | Tsutomu Takeuchi |
| collection | DOAJ |
| description | Objectives To investigate the long-term safety and efficacy of otilimab, an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody, for patients with rheumatoid arthritis (RA).Methods ContRAst X (NCT04333147) was a phase 3, multicentre, long-term extension trial. Patients with RA aged ≥18 years who completed a qualifying contRAst trial (contRAst 1–3) and who the investigator thought might benefit from long-term otilimab treatment were eligible to enter contRAst X. Patients who received otilimab (90 mg/150 mg) in their qualifying trial maintained the same dose; patients who received tofacitinib or sarilumab were rerandomised 1:1 to either otilimab dose. Patients could continue background conventional synthetic disease-modifying antirheumatic drugs. The primary objective was long-term safety (up to 4 years).Results Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination. For otilimab 90 mg and 150 mg, the incidence of adverse events (AEs) was 62% (n=902/1456) and 64% (n=931/1459), the incidence of AEs of special interest was 8% (n=120/1456) and 7% (n=95/1459) and the incidence of serious AEs was 8% (n=123/1456) and 8% (n=114/1459), respectively. There were no instances of pulmonary alveolar proteinosis (PAP), active tuberculosis (TB), TB reactivation or serious hypersensitivity reactions. The proportions of clinical disease activity index low disease activity responders remained relatively stable throughout, with no apparent reduction following the switch from tofacitinib/sarilumab to otilimab.Conclusion No new safety signals or instances of PAP were associated with long-term (≤2.5 years) treatment with otilimab.Trial registration number ClinicalTrials.gov: NCT04333147. |
| format | Article |
| id | doaj-art-76143a2e7d6941c290acfefe06b0d0c0 |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-76143a2e7d6941c290acfefe06b0d0c02025-08-20T03:02:05ZengBMJ Publishing GroupBMJ Open2044-60552025-03-0115310.1136/bmjopen-2024-088869Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X)Tsutomu Takeuchi0Iain B McInnes1Peter C Taylor2Roy M Fleischmann3Vibeke Strand4Michael E Weinblatt5David Brooks6Tatsuya Atsumi7Paula Curtis8Marguerite Bracher9Anubha Gupta10Didier Saurigny11Celia Shelton12Millie Wang13Reena Wang14Rina Nijhawan15Ciara O'Shea16Kirsty Rayner177 Saitama Medical University, Saitama, Japan3 College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK2 Botnar Research Centre, University of Oxford, Oxford, UK14 Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA5 Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA1 Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA9 GSK, Collegeville, Pennsylvania, USA4 Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan10 GSK, Brentford, Middlesex, UK8 GSK, Stevenage, Hertfordshire, UK8 GSK, Stevenage, Hertfordshire, UK8 GSK, Stevenage, Hertfordshire, UK9 GSK, Collegeville, Pennsylvania, USA10 GSK, Brentford, Middlesex, UK9 GSK, Collegeville, Pennsylvania, USA11 GSK, Durham, North Carolina, USA12 GSK, Dublin, Ireland10 GSK, Brentford, Middlesex, UKObjectives To investigate the long-term safety and efficacy of otilimab, an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody, for patients with rheumatoid arthritis (RA).Methods ContRAst X (NCT04333147) was a phase 3, multicentre, long-term extension trial. Patients with RA aged ≥18 years who completed a qualifying contRAst trial (contRAst 1–3) and who the investigator thought might benefit from long-term otilimab treatment were eligible to enter contRAst X. Patients who received otilimab (90 mg/150 mg) in their qualifying trial maintained the same dose; patients who received tofacitinib or sarilumab were rerandomised 1:1 to either otilimab dose. Patients could continue background conventional synthetic disease-modifying antirheumatic drugs. The primary objective was long-term safety (up to 4 years).Results Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination. For otilimab 90 mg and 150 mg, the incidence of adverse events (AEs) was 62% (n=902/1456) and 64% (n=931/1459), the incidence of AEs of special interest was 8% (n=120/1456) and 7% (n=95/1459) and the incidence of serious AEs was 8% (n=123/1456) and 8% (n=114/1459), respectively. There were no instances of pulmonary alveolar proteinosis (PAP), active tuberculosis (TB), TB reactivation or serious hypersensitivity reactions. The proportions of clinical disease activity index low disease activity responders remained relatively stable throughout, with no apparent reduction following the switch from tofacitinib/sarilumab to otilimab.Conclusion No new safety signals or instances of PAP were associated with long-term (≤2.5 years) treatment with otilimab.Trial registration number ClinicalTrials.gov: NCT04333147.https://bmjopen.bmj.com/content/15/3/e088869.full |
| spellingShingle | Tsutomu Takeuchi Iain B McInnes Peter C Taylor Roy M Fleischmann Vibeke Strand Michael E Weinblatt David Brooks Tatsuya Atsumi Paula Curtis Marguerite Bracher Anubha Gupta Didier Saurigny Celia Shelton Millie Wang Reena Wang Rina Nijhawan Ciara O'Shea Kirsty Rayner Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X) BMJ Open |
| title | Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X) |
| title_full | Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X) |
| title_fullStr | Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X) |
| title_full_unstemmed | Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X) |
| title_short | Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X) |
| title_sort | long term safety and efficacy of anti gm csf otilimab in patients with rheumatoid arthritis long term extension of three phase 3 randomised trials contrast x |
| url | https://bmjopen.bmj.com/content/15/3/e088869.full |
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