Subcutaneous IL-6 Inhibitor Sarilumab vs. Standard Care in Hospitalized Patients With Moderate-To-Severe COVID-19: An Open Label Randomized Clinical Trial

{ 'indexed': { 'date-parts': [[2023, 12, 23]], 'date-time': '2023-12-23T06:00:19Z', 'timestamp': 1703311219140}, 'reference-count': 36, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2022, 2, 23]], 'date-time': '2022-02-23T00:00:00Z', 'timestamp': 1645574400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100013412', 'name': 'Sanofi España', 'doi-asserted-by': 'publisher', 'id': [{'id': '10.13039/501100013412', 'id-type': 'DOI', 'asserted-by': 'publisher'}]}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>The use of IL-6 blockers in COVID-19 ' 'hospitalized patients has been associated with a reduction in mortality compared to standard ' 'care. However, many uncertainties remain pertaining to optimal intervention time, ' 'administration schedule, and predictors of response. To date, data on the use of subcutaneous ' 'sarilumab is limited and no randomized trial results are ' 'available.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Open label ' 'randomized controlled trial at a single center in Spain. We included adult patients admitted ' 'with microbiology documented COVID-19 infection, imaging confirmed pneumonia, fever and/or ' 'laboratory evidence of inflammatory phenotype, and no need for invasive ventilation. ' 'Participants were randomly assigned to receive sarilumab, a single 400 mg dose in two 200 mg ' 'subcutaneous injections, added to standard care or standard care, in a 2:1 proportion. ' 'Primary endpoints included 30-day mortality, mean change in clinical status at day 7 scored ' 'in a 7-category ordinal scale ranging from death (category 1) to discharge (category 7), and ' 'duration of hospitalization. The primary efficacy analysis was conducted on the ' 'intention-to-treat ' 'population.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of ' '30 patients underwent randomization: 20 to sarilumab and 10 to standard care. Most patients ' 'were male (20/30, 67%) with a median (interquartile range) age of 61.5 years (56–72). At day ' '30, 2/20 (10%) patients died in the sarilumab arm vs. none (0/10) in standard care (Log HR ' '15.11, SE 22.64; <jats:italic>p</jats:italic> = 0.54). At day 7, no significant differences ' 'were observed in the median change in clinical status (2 [0–3]) vs. 3 [0–3], ' '<jats:italic>p</jats:italic> = 0.32). Median time to discharge (days) was similar (7 [6–11] ' 'vs. 6 [4–12]; HR 0.65, SE 0.26; <jats:italic>p</jats:italic> = 0.27). No significant ' 'differences were detected in the rate of progression to invasive and noninvasive mechanical ' 'ventilation.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and ' 'Relevance</jats:title><jats:p>Our pragmatic pilot study has failed to demonstrate the benefit ' 'of adding subcutaneous sarilumab to standard care for mortality by 30 days, functional status ' 'at day 7, or hospital stay. Findings herein do not exclude a potential effect of sarilumab in ' 'severe COVID-19 but adequately powered blinded randomized phase III trials are warranted to ' 'assess the impact of the subcutaneous route and a more selected target ' 'population.</jats:p></jats:sec><jats:sec><jats:title>Trial ' 'Registration</jats:title><jats:p><jats:ext-link>www.ClinicalTrials</jats:ext-link>.gov, ' 'Identifier: NCT04357808.</jats:p></jats:sec>', 'DOI': '10.3389/fmed.2022.819621', 'type': 'journal-article', 'created': {'date-parts': [[2022, 2, 23]], 'date-time': '2022-02-23T12:24:29Z', 'timestamp': 1645619069000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 3, 'title': 'Subcutaneous IL-6 Inhibitor Sarilumab vs. Standard Care in Hospitalized Patients With ' 'Moderate-To-Severe COVID-19: An Open Label Randomized Clinical Trial', 'prefix': '10.3389', 'volume': '9', 'author': [ {'given': 'Rosario', 'family': 'García-Vicuña', 'sequence': 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