You are here

  • Home
  • Archive
  • Volume 15, Issue 3
  • 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)

Article Text

Article menu

Download PDFPDF

Rheumatology
Original research
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)
  1. Michael E Weinblatt1,
  2. Peter C Taylor2,
  3. Iain B McInnes3,
  4. Tatsuya Atsumi4,
  5. Vibeke Strand5,
  6. Tsutomu Takeuchi6,7,
  7. Marguerite Bracher8,
  8. David Brooks9,
  9. Paula Curtis10,
  10. Anubha Gupta8,
  11. Rina Nijhawan11,
  12. Ciara O'Shea12,
  13. Kirsty Rayner10,13,
  14. Didier Saurigny8,
  15. Celia Shelton9,
  16. Millie Wang10,
  17. Reena Wang9,
  18. Roy M Fleischmann14,15
  1. 1 Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  2. 2 Botnar Research Centre, University of Oxford, Oxford, UK
  3. 3 College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  4. 4 Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
  5. 5 Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA
  6. 6 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  7. 7 Saitama Medical University, Saitama, Japan
  8. 8 GSK, Stevenage, Hertfordshire, UK
  9. 9 GSK, Collegeville, Pennsylvania, USA
  10. 10 GSK, Brentford, Middlesex, UK
  11. 11 GSK, Durham, North Carolina, USA
  12. 12 GSK, Dublin, Ireland
  13. 13 Probabilitas Consulting Limited, Berkhamstead, UK
  14. 14 Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  15. 15 Metroplex Clinical Research Center, Dallas, Texas, USA
  1. Correspondence to Dr Michael E Weinblatt; mweinblatt{at}bwh.harvard.edu

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.

Trial registration number ClinicalTrials.gov: NCT04333147.

  • RHEUMATOLOGY
  • THERAPEUTICS
  • Clinical Trial

Data availability statement

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/.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi-org.ezproxy.u-pec.fr/10.1136/bmjopen-2024-088869

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    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/.

    View Full Text

    Footnotes

    • Contributors RMF contributed to the conception/design of the trial and the acquisition and analysis/interpretation of data. MEW, PCT, VS, MW, DS, AG, and DB contributed to the trial conception or design and data analysis or interpretation. IBMcI, TT, RW, KR, MB, RN, CS, CO’S and PC contributed to data analysis or interpretation. TA contributed to the acquisition of data and data analysis or interpretation. All authors contributed to drafting or critically revising the article and provided final approval and agreement of accountability. DS acted as guarantor.

    • Funding This trial (GSK ID: 209564) was funded by GSK.

    • Competing interests MEW receives research support from AbbVie, Aqtual, Bristol Myers Squibb and Lilly and consultation fees from AbbVie, Aclaris, Amgen, Bayer, Bristol Myers Squibb, CorEvitas, Genosco, Gilead Sciences, GSK, Horizon, Johnson & Johnson, Lilly, Novartis, Pfizer, Rami Therapeutics, R Pharma, Roche, Sanofi, Scipher, Sci Rhom, Set Point and Tremeau. He holds stock/stock options in CanFite, Inmedix and Scipher. PCT has received consulting fees from AbbVie, AnaptysBio, Acelyrin, Biogen, Immunovant, Fresenius, Galapagos, Gilead Sciences, GSK, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB and research support from Galapagos. IBMcI has received consultancy and research support from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway, Compugen, Gilead Sciences, GSK, Lilly, Novartis, Pfizer and UCB and holds a leadership role in the University of Glasgow, Versus Arthritis and is an NHS GGC Board Member and an Annals of the Rheumatic Diseases Editorial Board Member. TA has accepted research grants and/or honoraria for meetings from AbbVie, Alexion, Astellas Pharma, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Gilead Sciences, GSK, Lilly Japan, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer, Takeda Pharmaceutical and UCB Japan. VS has received consulting fees from AbbVie, Alpine, Alumis, Amgen, Aria, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Ermium, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kiniksa, Lilly, Merck, MiMedx, Novartis, Omeros, Pfizer, R-Pharm, RAPT, Regeneron, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, Tonix and Urica. TT received payment or honoraria from AbbVie, Asahi Kasei, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Gilead Sciences, Janssen, Lilly Japan, Mitsubishi-Tanabe and Pfizer Japan and is an Annals of the Rheumatic Diseases Editorial Board Member. MB, DB, PC, AG, RN, CO’S, DS, CS, MW and RW are employees of GSK and hold GSK stock/shares. KR is an employee of Probabilitas Consulting Limited and is contracted by GSK. RMF has received research support from AbbVie, Amgen, Arthrosi, AstraZeneca, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Galvani, Genentech/Roche, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Priovant, Samsung, Sanofi-Genzyme, Selecta and UCB; consulting fees from AbbVie, Amgen, Arthrosi, Bristol Myers Squibb, Cyxone, Dren Bio, Galapagos, Galvani, Gilead, GSK, Immunovant, ImmuneMed, InventisBio, Janssen, Kiniksa, Lilly, Monte Rosa, Novartis, Pfizer, Priovant, Recor, Samsung, Synact, UCB and VYNE and is an Annals of the Rheumatic Diseases Editorial Board Member.

    • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.