Effect of Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia: A Case-Control Cohort Study

DOI record: { "DOI": "10.3390/ph13100317", "ISSN": [ "1424-8247" ], "URL": "http://dx.doi.org/10.3390/ph13100317", "abstract": "<jats:p>Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO2 ≤ 96% despite O2-support ≥ 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 0.3–0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95%CI = 0.135–0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p &lt; 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.</jats:p>", "alternative-id": [ "ph13100317" ], "author": [ { "affiliation": [ { "name": "Department of Internal Medicine, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Rossi", "given": "Benjamin", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0002-6014-6269", "affiliation": [ { "name": "Research &amp; Innovation of CMC Ambroise Paré, 92200 Neuilly-Sur-Seine, France" }, { "name": "INSERM, Clinical Investigations Center Paris-Est, CIC-1901, Sorbonne Université, AP.HP. Pitié-Salpétrière, 75013 Paris, France" } ], "authenticated-orcid": false, "family": "Nguyen", "given": "Lee S.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-8772-1596", "affiliation": [ { "name": "Department of Pharmacy, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "authenticated-orcid": false, "family": "Zimmermann", "given": "Philippe", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Boucenna", "given": "Faiza", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pharmacy, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Dubret", "given": "Louis", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Baucher", "given": "Louise", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Guillot", "given": "Helene", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Bouldouyre", "given": "Marie-Anne", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine and Clinical Immunology, Sorbonne Université, AP.HP. Pitié-Salpétrière, 75013 Paris, France" } ], "family": "Allenbach", "given": "Yves", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-0331-3307", "affiliation": [ { "name": "INSERM, Clinical Investigations Center Paris-Est, CIC-1901, Sorbonne Université, AP.HP. Pitié-Salpétrière, 75013 Paris, France" } ], "authenticated-orcid": false, "family": "Salem", "given": "Joe-Elie", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Cardiology, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Barsoum", "given": "Paul", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pharmacy, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Oufella", "given": "Arezki", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Robert Ballanger Hospital, 93600 Aulnay-Sous-Bois, France" } ], "family": "Gros", "given": "Helene", "sequence": "additional" } ], "container-title": "Pharmaceuticals", "container-title-short": "Pharmaceuticals", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 10, 17 ] ], "date-time": "2020-10-17T11:23:22Z", "timestamp": 1602933802000 }, "deposited": { "date-parts": [ [ 2024, 7, 4 ] ], "date-time": "2024-07-04T09:12:50Z", "timestamp": 1720084370000 }, "indexed": { "date-parts": [ [ 2025, 2, 21 ] ], "date-time": "2025-02-21T16:34:22Z", "timestamp": 1740155662954, "version": "3.37.3" }, "is-referenced-by-count": 26, "issue": "10", "issued": { "date-parts": [ [ 2020, 10, 17 ] ] }, "journal-issue": { "issue": "10", "published-online": { "date-parts": [ [ 2020, 10 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 10, 17 ] ], "date-time": "2020-10-17T00:00:00Z", "timestamp": 1602892800000 } } ], "link": [ { "URL": "https://www.mdpi.com/1424-8247/13/10/317/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "317", "prefix": "10.3390", "published": { "date-parts": [ [ 2020, 10, 17 ] ] }, "published-online": { "date-parts": [ [ 2020, 10, 17 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.2807/1560-7917.ES.2020.25.9.2000178", "doi-asserted-by": "crossref", "key": "ref_1", "unstructured": "Spiteri, G., Fielding, J., Diercke, M., Campese, C., Enouf, V., Gaymard, A., Bella, A., Sognamiglio, P., Sierra Moros, M.J., and Riutort, A.N. (2020). First Cases of Coronavirus Disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020. Eurosurveillance, 25." }, { "DOI": "10.1001/jama.2020.5394", "article-title": "Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy", "author": "Grasselli", "doi-asserted-by": "crossref", "first-page": "1574", "journal-title": "JAMA", "key": "ref_2", "volume": "323", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)30628-0", "article-title": "COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression", "author": "Mehta", "doi-asserted-by": "crossref", "first-page": "1033", "journal-title": "Lancet", "key": "ref_3", "volume": "395", "year": "2020" }, { "DOI": "10.1634/theoncologist.2018-0028", "article-title": "FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome", "author": "Le", "doi-asserted-by": "crossref", "first-page": "943", "journal-title": "Oncologist", "key": "ref_4", "volume": "23", "year": "2018" }, { "DOI": "10.1016/j.jaut.2020.102452", "article-title": "Can We Use Interleukin-6 (IL-6) Blockade for Coronavirus Disease 2019 (COVID-19)-Induced Cytokine Release Syndrome (CRS)?", "author": "Liu", "doi-asserted-by": "crossref", "first-page": "102452", "journal-title": "J. Autoimmun.", "key": "ref_5", "volume": "111", "year": "2020" }, { "DOI": "10.1016/j.ijantimicag.2020.105954", "article-title": "Cytokine Release Syndrome in Severe COVID-19: Interleukin-6 Receptor Antagonist Tocilizumab May Be the Key to Reduce Mortality", "author": "Zhang", "doi-asserted-by": "crossref", "first-page": "105954", "journal-title": "Int. J. Antimicrob. Agents", "key": "ref_6", "volume": "55", "year": "2020" }, { "DOI": "10.1001/jama.2020.6775", "article-title": "Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area", "author": "Richardson", "doi-asserted-by": "crossref", "first-page": "2052", "journal-title": "JAMA", "key": "ref_7", "volume": "323", "year": "2020" }, { "DOI": "10.1001/jamanetworkopen.2020.6785", "article-title": "Epidemiological Assessment of Imported Coronavirus Disease 2019 (COVID-19) Cases in the Most Affected City Outside of Hubei Province, Wenzhou, China", "author": "Han", "doi-asserted-by": "crossref", "first-page": "e206785", "journal-title": "JAMA Netw. Open", "key": "ref_8", "volume": "3", "year": "2020" }, { "DOI": "10.1016/S2665-9913(20)30164-8", "article-title": "Anakinra for Severe Forms of COVID-19: A Cohort Study", "author": "Huet", "doi-asserted-by": "crossref", "first-page": "e393", "journal-title": "Lancet Rheumatol.", "key": "ref_9", "volume": "2", "year": "2020" }, { "key": "ref_10", "unstructured": "The RECOVERY Collaborative Group (2020). Dexamethasone in Hospitalized Patients with Covid-19—Preliminary Report. N. Engl. J. Med." }, { "DOI": "10.1101/2020.06.22.20137273", "doi-asserted-by": "crossref", "key": "ref_11", "unstructured": "Horby, P., Lim, W.S., Emberson, J., Mafham, M., Bell, J., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., and Elmahi, E. (2020). Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report. Infect. Dis." }, { "DOI": "10.1016/j.autrev.2020.102568", "article-title": "Tocilizumab for the Treatment of Severe COVID-19 Pneumonia with Hyperinflammatory Syndrome and Acute Respiratory Failure: A Single Center Study of 100 Patients in Brescia, Italy", "author": "Toniati", "doi-asserted-by": "crossref", "first-page": "102568", "journal-title": "Autoimmun. Rev.", "key": "ref_12", "volume": "19", "year": "2020" }, { "DOI": "10.1016/S2665-9913(20)30173-9", "article-title": "Tocilizumab in Patients with Severe COVID-19: A Retrospective Cohort Study", "author": "Guaraldi", "doi-asserted-by": "crossref", "first-page": "e474", "journal-title": "Lancet Rheumatol.", "key": "ref_13", "volume": "2", "year": "2020" }, { "key": "ref_14", "unstructured": "(2020, October 15). CORIMUNO-19-Tocilizumab Trial-TOCI (CORIMUNO-TOCI), Available online: https://clinicaltrials.gov/ct2/show/NCT04331808201202317." }, { "key": "ref_15", "unstructured": "(2020, October 15). A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia (COVACTA), Available online: https://clinicaltrials.gov/ct2/show/NCT04320615." }, { "DOI": "10.1007/s10067-011-1936-6", "article-title": "Access to the next Wave of Biologic Therapies (Abatacept and Tocilizumab) for the Treatment of Rheumatoid Arthritis in England and Wales: Addressing Treatment Outside the Current NICE Guidance", "author": "Chiu", "doi-asserted-by": "crossref", "first-page": "1005", "journal-title": "Clin. Rheumatol.", "key": "ref_16", "volume": "31", "year": "2012" }, { "DOI": "10.1002/jcph.826", "article-title": "Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis From 2 Randomized, Controlled Trials: SUMMACTA and BREVACTA: Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous", "author": "Abdallah", "doi-asserted-by": "crossref", "first-page": "459", "journal-title": "J. Clin. Pharmacol.", "key": "ref_17", "volume": "57", "year": "2017" }, { "DOI": "10.1002/sim.1903", "article-title": "Stratification and Weighting via the Propensity Score in Estimation of Causal Treatment Effects: A Comparative Study", "author": "Lunceford", "doi-asserted-by": "crossref", "first-page": "2937", "journal-title": "Stat. Med.", "key": "ref_18", "volume": "23", "year": "2004" }, { "DOI": "10.1177/0962280215584401", "article-title": "The Performance of Inverse Probability of Treatment Weighting and Full Matching on the Propensity Score in the Presence of Model Misspecification When Estimating the Effect of Treatment on Survival Outcomes", "author": "Austin", "doi-asserted-by": "crossref", "first-page": "1654", "journal-title": "Stat. Methods Med. Res.", "key": "ref_19", "volume": "26", "year": "2017" }, { "DOI": "10.15171/jcvtr.2014.06", "article-title": "Comparison of the Spo2 /Fio2 Ratio and the Pao 2 /Fio 2 Ratio in Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome", "author": "Bilan", "doi-asserted-by": "crossref", "first-page": "28", "journal-title": "J. Cardiovasc. Thorac. Res.", "key": "ref_20", "volume": "7", "year": "2015" }, { "DOI": "10.1016/j.chest.2020.04.003", "article-title": "The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic", "author": "Rubin", "doi-asserted-by": "crossref", "first-page": "106", "journal-title": "Chest", "key": "ref_21", "volume": "158", "year": "2020" } ], "reference-count": 21, "references-count": 21, "relation": { "has-preprint": [ { "asserted-by": "object", "id": "10.1101/2020.06.06.20122341", "id-type": "doi" } ] }, "resource": { "primary": { "URL": "https://www.mdpi.com/1424-8247/13/10/317" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Effect of Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia: A Case-Control Cohort Study", "type": "journal-article", "volume": "13" }