RT Journal Article
SR Electronic
T1 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)
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e088869
DO 10.1136/bmjopen-2024-088869
VO 15
IS 3
A1 Weinblatt, Michael E
A1 Taylor, Peter C
A1 McInnes, Iain B
A1 Atsumi, Tatsuya
A1 Strand, Vibeke
A1 Takeuchi, Tsutomu
A1 Bracher, Marguerite
A1 Brooks, David
A1 Curtis, Paula
A1 Gupta, Anubha
A1 Nijhawan, Rina
A1 O'Shea, Ciara
A1 Rayner, Kirsty
A1 Saurigny, Didier
A1 Shelton, Celia
A1 Wang, Millie
A1 Wang, Reena
A1 Fleischmann, Roy M
YR 2025
UL http://bmjopen.bmj.com/content/15/3/e088869.abstract
AB 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Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination.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.Data are available upon reasonable request. GSK has a long-standing commitment to clinical data transparency. The GSK Study Register is an online portal where anyone can access information about the clinical research GSK carries out on its existing vaccines and medicines. GSK registers protocol summaries before the start of a trial and posts results summaries within a year of study completion. Since 2020, GSK has developed plain language summaries of the results of our phase 2–4 clinical trials, which are shared with the study investigator for distribution to trial participants and are available on the GSK Study Register and www.trialsummaries.com. GSK is committed to providing access to anonymised patient-level data that sit behind the results of clinical trials. GSK-sponsored interventional clinical trials will be listed for data sharing once a medicine has been approved by regulators or terminated from development, and the study has been accepted for publication. External researchers can request access to anonymised patient-level clinical trial data and supporting clinical trial documents through the multisponsor data-sharing portals. Further details are available at: http://www.gsk.com/en-gb/innovation/trials/data-transparency/ and http://www.gsk-studyregister.com/en/.