tetano
Editor, Senior Moderator
Eur Respir J
. 2022 Oct 13;2101870.
doi: 10.1183/13993003.01870-2021. Online ahead of print.
A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR)
Jatin Patel[SUP] 1 [/SUP], Damon Bass[SUP] 2 [/SUP], Albertus Beishuizen[SUP] 3 [/SUP], Xavier Bocca Ruiz[SUP] 4 [/SUP], Hatem Boughanmi[SUP] 5 [/SUP], Anthony Cahn[SUP] 6 [/SUP], Hugo Colombo[SUP] 7 [/SUP], Gerard J Criner[SUP] 8 [/SUP], Katherine Davy[SUP] 1 [/SUP], Javier de-Miguel-Díez[SUP] 9 10 [/SUP], Pablo A Doreski[SUP] 11 [/SUP], Sofia Fernandes[SUP] 1 [/SUP], Bruno François[SUP] 12 [/SUP], Anubha Gupta[SUP] 1 [/SUP], Kate Hanrott[SUP] 1 [/SUP], Timothy Hatlen[SUP] 13 [/SUP], Dave Inman[SUP] 1 [/SUP], John D Isaacs[SUP] 14 [/SUP], Emily Jarvis[SUP] 1 [/SUP], Natalia Kostina[SUP] 15 [/SUP], Tatiana Kropotina[SUP] 16 [/SUP], Jean-Claude Lacherade[SUP] 17 [/SUP], Divya Lakshminarayanan[SUP] 18 [/SUP], Pedro Martinez-Ayala[SUP] 19 [/SUP], Charlene McEvoy[SUP] 20 21 22 [/SUP], Ferhat Meziani[SUP] 23 24 [/SUP], Mehran Monchi[SUP] 25 [/SUP], Sumanta Mukherjee[SUP] 18 [/SUP], Rosana Muñoz-Bermúdez[SUP] 26 [/SUP], Jessica Neisen[SUP] 1 27 [/SUP], Ciara O'Shea[SUP] 28 [/SUP], Gaëtan Plantefeve[SUP] 29 [/SUP], Lorrie Schifano[SUP] 2 [/SUP], Lee E Schwab[SUP] 30 [/SUP], Zainab Shahid[SUP] 31 [/SUP], Michinori Shirano[SUP] 32 [/SUP], Julia E Smith[SUP] 1 [/SUP], Eduardo Sprinz[SUP] 33 [/SUP], Charlotte Summers[SUP] 34 [/SUP], Nicolas Terzi[SUP] 35 36 37 [/SUP], Mark A Tidswell[SUP] 38 [/SUP], Yuliya Trefilova[SUP] 39 [/SUP], Russell Williamson[SUP] 1 27 [/SUP], Duncan Wyncoll[SUP] 40 [/SUP], Mark Layton[SUP] 1 [/SUP]
Affiliations
Abstract
Abstract BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (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
lacebo), 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 CCL17, 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.
. 2022 Oct 13;2101870.
doi: 10.1183/13993003.01870-2021. Online ahead of print.
A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR)
Jatin Patel[SUP] 1 [/SUP], Damon Bass[SUP] 2 [/SUP], Albertus Beishuizen[SUP] 3 [/SUP], Xavier Bocca Ruiz[SUP] 4 [/SUP], Hatem Boughanmi[SUP] 5 [/SUP], Anthony Cahn[SUP] 6 [/SUP], Hugo Colombo[SUP] 7 [/SUP], Gerard J Criner[SUP] 8 [/SUP], Katherine Davy[SUP] 1 [/SUP], Javier de-Miguel-Díez[SUP] 9 10 [/SUP], Pablo A Doreski[SUP] 11 [/SUP], Sofia Fernandes[SUP] 1 [/SUP], Bruno François[SUP] 12 [/SUP], Anubha Gupta[SUP] 1 [/SUP], Kate Hanrott[SUP] 1 [/SUP], Timothy Hatlen[SUP] 13 [/SUP], Dave Inman[SUP] 1 [/SUP], John D Isaacs[SUP] 14 [/SUP], Emily Jarvis[SUP] 1 [/SUP], Natalia Kostina[SUP] 15 [/SUP], Tatiana Kropotina[SUP] 16 [/SUP], Jean-Claude Lacherade[SUP] 17 [/SUP], Divya Lakshminarayanan[SUP] 18 [/SUP], Pedro Martinez-Ayala[SUP] 19 [/SUP], Charlene McEvoy[SUP] 20 21 22 [/SUP], Ferhat Meziani[SUP] 23 24 [/SUP], Mehran Monchi[SUP] 25 [/SUP], Sumanta Mukherjee[SUP] 18 [/SUP], Rosana Muñoz-Bermúdez[SUP] 26 [/SUP], Jessica Neisen[SUP] 1 27 [/SUP], Ciara O'Shea[SUP] 28 [/SUP], Gaëtan Plantefeve[SUP] 29 [/SUP], Lorrie Schifano[SUP] 2 [/SUP], Lee E Schwab[SUP] 30 [/SUP], Zainab Shahid[SUP] 31 [/SUP], Michinori Shirano[SUP] 32 [/SUP], Julia E Smith[SUP] 1 [/SUP], Eduardo Sprinz[SUP] 33 [/SUP], Charlotte Summers[SUP] 34 [/SUP], Nicolas Terzi[SUP] 35 36 37 [/SUP], Mark A Tidswell[SUP] 38 [/SUP], Yuliya Trefilova[SUP] 39 [/SUP], Russell Williamson[SUP] 1 27 [/SUP], Duncan Wyncoll[SUP] 40 [/SUP], Mark Layton[SUP] 1 [/SUP]
Affiliations
- PMID: 36229048
- DOI: 10.1183/13993003.01870-2021
Abstract
Abstract BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (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
lacebo), 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 CCL17, 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.