A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)

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• dc.contributor.author Patel, Jatin
• dc.contributor.author Muñoz-Bermúdez, Rosana
• dc.contributor.author Layton, Mark
• dc.date.accessioned 2023-03-30T06:00:14Z
• dc.date.available 2023-03-30T06:00:14Z
• dc.date.issued 2023
• dc.description.abstract Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. Methods: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. Results: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. Conclusions: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.
• dc.format.mimetype application/pdf
• dc.identifier.citation Patel J, Bass D, Beishuizen A, Bocca Ruiz X, Boughanmi H, Cahn A, et al. A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR). Eur Respir J. 2023 Feb 2;61(2):2101870. DOI: 10.1183/13993003.01870-2021
• dc.identifier.doi http://dx.doi.org/10.1183/13993003.01870-2021
• dc.identifier.issn 0903-1936
• dc.identifier.uri http://hdl.handle.net/10230/56376
• dc.language.iso eng
• dc.publisher European Respiratory Society
• dc.relation.ispartof Eur Respir J. 2023 Feb 2;61(2):2101870
• dc.rights © The authors 2023. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.title A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion