PT  - JOURNAL ARTICLE
AU  - Jatin Patel
AU  - Damon Bass
AU  - Albertus Beishuizen
AU  - Xavier Bocca Ruiz
AU  - Hatem Boughanmi
AU  - Anthony Cahn
AU  - Hugo Colombo
AU  - Gerard J. Criner
AU  - Katherine Davy
AU  - Javier de-Miguel-Díez
AU  - Pablo A. Doreski
AU  - Sofia Fernandes
AU  - Bruno François
AU  - Anubha Gupta
AU  - Kate Hanrott
AU  - Timothy Hatlen
AU  - Dave Inman
AU  - John D. Isaacs
AU  - Emily Jarvis
AU  - Natalia Kostina
AU  - Tatiana Kropotina
AU  - Jean-Claude Lacherade
AU  - Divya Lakshminarayanan
AU  - Pedro Martinez-Ayala
AU  - Charlene McEvoy
AU  - Ferhat Meziani
AU  - Mehran Monchi
AU  - Sumanta Mukherjee
AU  - Rosana Muñoz-Bermúdez
AU  - Jessica Neisen
AU  - Ciara O'Shea
AU  - Gaëtan Plantefeve
AU  - Lorrie Schifano
AU  - Lee E. Schwab
AU  - Zainab Shahid
AU  - Michinori Shirano
AU  - Julia E. Smith
AU  - Eduardo Sprinz
AU  - Charlotte Summers
AU  - Nicolas Terzi
AU  - Mark A. Tidswell
AU  - Yuliya Trefilova
AU  - Russell Williamson
AU  - Duncan Wyncoll
AU  - Mark Layton
TI  - A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)
AID  - 10.1183/13993003.01870-2021
DP  - 2023 Feb 01
TA  - European Respiratory Journal
PG  - 2101870
VI  - 61
IP  - 2
4099  - http://erj.ersjournals.com/content/61/2/2101870.short
4100  - http://erj.ersjournals.com/content/61/2/2101870.full
SO  - Eur Respir J2023 Feb 01; 61
AB  - 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.Therapeutic blocking of GM-CSF with otilimab did not significantly improve clinical status in patients with severe COVID-19; however, otilimab demonstrated an acceptable safety profile and reduced markers of inflammation https://bit.ly/3QquyYP