{"doi":"10.1371/journal.pone.0270668","title":"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis","abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background</jats:title>\n                    <jats:p>A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods</jats:title>\n                    <jats:p>Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation.</jats:p>\n                    <jats:p>Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Findings</jats:title>\n                    <jats:p>One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71–0·95, p = 0·008]] and sarilumab [0·80 [0·61–1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81–1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.</jats:p>\n                  </jats:sec>","journal":"PLOS ONE","year":2022,"id":606992,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1274841,"name":"David J. Fisher","orcid":"0000-0002-2512-2296","position":1,"is_corresponding":false},{"id":802942,"name":"Lindsay R. Berry","orcid":"0009-0003-4782-2570","position":2,"is_corresponding":false},{"id":1558450,"name":"Lennie P. G. Derde","orcid":null,"position":3,"is_corresponding":false},{"id":1558451,"name":"Janet V. Diaz","orcid":null,"position":4,"is_corresponding":false},{"id":3860,"name":"Anthony C. Gordon","orcid":"0000-0002-0419-547X","position":5,"is_corresponding":false},{"id":802941,"name":"Elizabeth Lorenzi","orcid":"0000-0002-7259-2696","position":6,"is_corresponding":false},{"id":15376,"name":"John C. Marshall","orcid":"0000-0002-7902-6291","position":7,"is_corresponding":false},{"id":3884,"name":"Srinivas Murthy","orcid":"0000-0002-9476-839X","position":8,"is_corresponding":false},{"id":1552787,"name":"Manu Shankar-Hari","orcid":null,"position":9,"is_corresponding":false},{"id":2304,"name":"Jonathan A. C. Sterne","orcid":"0000-0001-8496-6053","position":10,"is_corresponding":false},{"id":1163277,"name":"Jayne F. Tierney","orcid":"0000-0002-4734-3014","position":11,"is_corresponding":false},{"id":1274840,"name":"Claire L. Vale","orcid":"0000-0001-5157-0634","position":12,"is_corresponding":false},{"id":1163274,"name":"Peter J. Godolphin","orcid":"0000-0003-0648-0992","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis","abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background</jats:title>\n                    <jats:p>A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods</jats:title>\n                    <jats:p>Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation.</jats:p>\n                    <jats:p>Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Findings</jats:title>\n                    <jats:p>One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71–0·95, p = 0·008]] and sarilumab [0·80 [0·61–1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81–1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35802687","pmcid":"PMC9269978","openalex_id":"https://openalex.org/W4284970605","authors":[],"funders":[{"funder_name":"Prostate Cancer UK","grant_id":"RIA 16-ST2-020","title":null},{"funder_name":"National Institute for Health Research","grant_id":"NIHR301653","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_00004/06","title":"Method Meta-analysis"},{"funder_name":"National Institute for Health Research","grant_id":"NIHR-CS-2016-16-011","title":null},{"funder_name":"School for Social Care Research","grant_id":"RP-2015-06-018","title":null},{"funder_name":"World Health Organization","grant_id":"001","title":null},{"funder_name":"National Institute for Health Research (NIHR)","grant_id":"Covid-19 - REMAP-CAP","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"},{"funder_name":"European Commission","grant_id":"101003589","title":"Rapid European SARS-CoV-2 Emergency research Response"}],"total_grants":9,"fwci":2.5114,"citation_percentile":0.91399564,"influential_citations":0,"citation_trend":[{"year":2022,"count":5},{"year":2023,"count":11},{"year":2024,"count":6},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1371/journal.pone.0270668","host_type":"journal"},{"url":"https://doi.org/10.1371/journal.pone.0270668","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pone.0270668","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35802687","host_type":"repository"},{"url":"https://www.research.ed.ac.uk/en/publications/cb7589e8-1fdd-4c69-b5a7-d7437a7cc71b","host_type":"repository"},{"url":"https://research-information.bris.ac.uk/en/publications/8e2d98c1-8a35-4839-878b-d6c66590313f","host_type":"repository"},{"url":"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270668","host_type":"repository"},{"url":"https://doaj.org/article/2a17726258534f749bc1365f6a1b21eb","host_type":"repository"},{"url":"https://dspace.library.uu.nl/handle/1874/448256","host_type":"repository"},{"url":"https://discovery.ucl.ac.uk/id/eprint/10151879/","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9269978","host_type":"repository"},{"url":"https://hdl.handle.net/1983/8e2d98c1-8a35-4839-878b-d6c66590313f","host_type":"repository"},{"url":"http://hdl.handle.net/10044/1/98463","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9269978","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9269978?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2021.08.26.21262523","host_type":""},{"url":"https://www.medrxiv.org/content/medrxiv/early/2021/08/28/2021.08.26.21262523.full.pdf","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pone.0270668","host_type":""},{"url":"https://dx.doi.org/10.1101/2021.08.26.21262523","host_type":""},{"url":"https://research-information.bris.ac.uk/ws/files/337846178/journal.pone.0270668_1_.pdf","host_type":""},{"url":"https://www.pure.ed.ac.uk/ws/files/292722853/journal.pone.0270668_1_.pdf","host_type":""},{"url":"https://hdl.handle.net/20.500.11820/cb7589e8-1fdd-4c69-b5a7-d7437a7cc71b","host_type":""},{"url":"https://discovery-pp.ucl.ac.uk/id/eprint/10151879/","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pone.0270668","host_type":""}],"fields_of_study":["COVID-19 Clinical Research Studies","Long-Term Effects of COVID-19","Adrenal Hormones and Disorders","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Network Meta-Analysis","COVID-19 Drug Treatment","Adrenal Cortex Hormones","Humans","Prospective Studies","Randomized Controlled Trials as Topic","Antibodies, Monoclonal, Humanized"],"keywords":["Tocilizumab","Medicine","Placebo","Meta-analysis","Concomitant","Internal medicine","Coronavirus disease 2019 (COVID-19)","Randomized controlled trial","Emergency medicine","Rheumatoid arthritis","Alternative medicine","General Science & Technology","Science","Q","R","610","Antibodies, Monoclonal, Humanized","COVID-19 Drug Treatment","Adrenal Cortex Hormones","616","Humans","Prospective Studies","Research Article","Randomized Controlled Trials as Topic"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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