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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)

Abstract:

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Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination.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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/bmjopen-2024-088869

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Kennedy Institute for Rheumatology
Oxford college:
St Peter's College
Role:
Author
ORCID:
0000-0001-7766-6167


Publisher:
BMJ Publishing Group
Journal:
BMJ Open More from this journal
Volume:
15
Article number:
e088869
Publication date:
2025-03-05
Acceptance date:
2025-01-20
DOI:
EISSN:
2044-6055
ISSN:
2044-6055


Language:
English
Pubs id:
2080210
Local pid:
pubs:2080210
Deposit date:
2025-01-23
ARK identifier:

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