{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:39:30Z","timestamp":1790015970500,"version":"4.0.1"},"reference-count":39,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2022,8,24]]},"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18\u201379\u2005years (Part 1) or \u226570\u2005years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein\/ferritin) received a single intravenous infusion of otilimab 90\u2005mg (human anti-GM-CSF monoclonal antibody) plus standard care (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04376684\">NCT04376684<\/jats:ext-link>\n                      ). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>versus<\/jats:italic>\n                      67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI \u22120.8\u201311.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2\u201333.1%, p=0.009) was observed in the predefined 70\u201379\u2005years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI \u22129.3\u201311.2%, 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.01870-2021","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T09:00:30Z","timestamp":1665651630000},"page":"2101870","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia 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