Late onset infectious complications and safety of tocilizumab in the management of COVID‐19

Pettit et al., Journal of Medical Virology, doi:10.1002/jmv.26429, Aug 2020

https://c19early.org/pettit.html

Retrospective 74 hospitalized COVID-19 patients treated with tocilizumab and 74 matched controls, showing higher mortality with tocilizumab.

Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments1. Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments. This may explain in part the very high mortality seen in this study. Results may differ in countries with improved SOC.

Important missing comments or errors? Let us know.

risk of death, 70.6% higher, RR 1.71, p = 0.05, treatment 29 of 74 (39.2%), control 17 of 74 (23.0%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. c19early.org, c19early.org/soc/usa.html.c19early.org/soc/usa.html.

Pettit et al., 21 Aug 2020, retrospective, USA, peer-reviewed, 7 authors, study period 1 March, 2020 - 25 April, 2020.

This Paper Tocilizumab All

DOI record: { "DOI": "10.1002/jmv.26429", "ISSN": [ "0146-6615", "1096-9071" ], "URL": "http://dx.doi.org/10.1002/jmv.26429", "abstract": "AbstractBackgroundTocilizumab (TCZ) has been used in the management of COVID‐19‐related cytokine release syndrome (CRS). Concerns exist regarding the risk of infections and drug‐related toxicities. We sought to evaluate the incidence of these TCZ complications among COVID‐19 patients.MethodsAll adult inpatients with COVID‐19 between 1 March and 25 April 2020 that received TCZ were included. We compared the rate of late‐onset infections (>48 hours following admission) to a control group matched according to intensive care unit admission and mechanical ventilation requirement. Post‐TCZ toxicities evaluated included: elevated liver function tests (LFTs), GI perforation, diverticulitis, neutropenia, hypertension, allergic reactions, and infusion‐related reactions.ResultsSeventy‐four patients were included in each group. Seventeen infections in the TCZ group (23%) and 6 (8%) infections in the control group occurred >48 hours after admission (P = .013). Most infections were bacterial with pneumonia being the most common manifestation. Among patients receiving TCZ, LFT elevations were observed in 51%, neutropenia in 1.4%, and hypertension in 8%. The mortality rate among those that received TCZ was greater than the control (39% versus 23%, P = .03).ConclusionLate onset infections were significantly more common among those receiving TCZ. Combining infections and TCZ‐related toxicities, 61% of patients had a possible post‐TCZ complication. While awaiting clinical trial results to establish the efficacy of TCZ for COVID‐19 related CRS, the potential for infections and TCZ related toxicities should be carefully weighed when considering use.", "alternative-id": [ "10.1002/jmv.26429" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2020-06-30" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 1, "value": "2020-08-10" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 2, "value": "2020-08-21" } ], "author": [ { "ORCID": "https://orcid.org/0000-0002-8937-8039", "affiliation": [ { "name": "Department of Pharmacy University of Chicago Medicine Chicago Illinois" } ], "authenticated-orcid": false, "family": "Pettit", "given": "Natasha N.", "sequence": "first" }, { "affiliation": [ { "name": "Department of Pharmacy University of Chicago Medicine Chicago Illinois" } ], "family": "Nguyen", "given": "Cynthia T.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago Medicine Chicago Illinois" } ], "family": "Mutlu", "given": "Gökhan M.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago Medicine Chicago Illinois" } ], "family": "Wu", "given": "David", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago Medicine Chicago Illinois" } ], "family": "Kimmig", "given": "Lucas", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medicine, Section of Infectious Diseases and Global Health University of Chicago Medicine Chicago Illinois" } ], "family": "Pitrak", "given": "David", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medicine, Section of Infectious Diseases and Global Health University of Chicago Medicine Chicago Illinois" } ], "family": "Pursell", "given": "Kenneth", "sequence": "additional" } ], "container-title": "Journal of Medical Virology", "container-title-short": "Journal of Medical Virology", "content-domain": { "crossmark-restriction": true, "domain": [ "onlinelibrary.wiley.com" ] }, "created": { "date-parts": [ [ 2020, 8, 13 ] ], "date-time": "2020-08-13T13:39:23Z", "timestamp": 1597325963000 }, "deposited": { "date-parts": [ [ 2023, 8, 28 ] ], "date-time": "2023-08-28T03:52:22Z", "timestamp": 1693194742000 }, "indexed": { "date-parts": [ [ 2025, 5, 29 ] ], "date-time": "2025-05-29T17:24:45Z", "timestamp": 1748539485355, "version": "3.37.3" }, "is-referenced-by-count": 61, "issue": "3", "issued": { "date-parts": [ [ 2020, 8, 21 ] ] }, "journal-issue": { "issue": "3", "published-print": { "date-parts": [ [ 2021, 3 ] ] } }, "language": "en", "license": [ { "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 8, 21 ] ], "date-time": "2020-08-21T00:00:00Z", "timestamp": 1597968000000 } } ], "link": [ { "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjmv.26429", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26429", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmv.26429", "content-type": "application/xml", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26429", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "311", "original-title": [], "page": "1459-1464", "prefix": "10.1002", "published": { "date-parts": [ [ 2020, 8, 21 ] ] }, "published-online": { "date-parts": [ [ 2020, 8, 21 ] ] }, "published-print": { "date-parts": [ [ 2021, 3 ] ] }, "publisher": "Wiley", "reference": [ { "DOI": "10.1093/cid/ciaa449", "doi-asserted-by": "publisher", "key": "e_1_2_8_2_1" }, { "DOI": "10.1016/j.jaut.2020.102433", "doi-asserted-by": "publisher", "key": "e_1_2_8_3_1" }, { "DOI": "10.1073/pnas.2005615117", "doi-asserted-by": "publisher", "key": "e_1_2_8_4_1" }, { "DOI": "10.1016/j.ijantimicag.2020.106043", "doi-asserted-by": "publisher", "key": "e_1_2_8_5_1" }, { "DOI": "10.1002/jmv.25801", "doi-asserted-by": "publisher", "key": "e_1_2_8_6_1" }, { "DOI": "10.1016/j.ejim.2020.05.011", "doi-asserted-by": "publisher", "key": "e_1_2_8_7_1" }, { "DOI": "10.1016/j.autrev.2020.102568", "doi-asserted-by": "publisher", "key": "e_1_2_8_8_1" }, { "DOI": "10.1016/j.ejim.2020.05.021", "doi-asserted-by": "publisher", "key": "e_1_2_8_9_1" }, { "DOI": "10.1080/21645515.2017.1316909", "doi-asserted-by": "publisher", "key": "e_1_2_8_10_1" }, { "DOI": "10.1016/j.autrev.2020.102564", "doi-asserted-by": "publisher", "key": "e_1_2_8_11_1" }, { "DOI": "10.1001/jama.2020.6775", "doi-asserted-by": "publisher", "key": "e_1_2_8_12_1" }, { "DOI": "10.1016/S0140-6736(20)30566-3", "doi-asserted-by": "publisher", "key": "e_1_2_8_13_1" }, { "DOI": "10.1016/S0140-6736(20)30183-5", "doi-asserted-by": "publisher", "key": "e_1_2_8_14_1" }, { "DOI": "10.1016/S2213-2600(20)30079-5", "doi-asserted-by": "publisher", "key": "e_1_2_8_15_1" }, { "DOI": "10.1001/jama.2020.3204", "doi-asserted-by": "publisher", "key": "e_1_2_8_16_1" }, { "DOI": "10.1056/NEJMoa2004500", "doi-asserted-by": "publisher", "key": "e_1_2_8_17_1" }, { "key": "e_1_2_8_18_1", "unstructured": "Tocilizumab (Actemra®) Prescribing Information. South San Francisco CA: Genentech Inc. Revised October 2013." }, { "DOI": "10.1046/j.1365-280X.1999.00247.x", "doi-asserted-by": "publisher", "key": "e_1_2_8_19_1" }, { "DOI": "10.1136/bmj.m1966", "doi-asserted-by": "publisher", "key": "e_1_2_8_20_1" }, { "key": "e_1_2_8_21_1", "unstructured": "National Center for Immunization and Respiratory Disease (NCIRD). Division of Viral Diseases.Evidence Used to Update the List of Underlying Medical Conditions that Increase a Persons Risk of Severe Illness from COVID‐19.https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/evidence-table.html. Accessed June 25 2020." }, { "DOI": "10.1001/jama.2020.8630", "doi-asserted-by": "publisher", "key": "e_1_2_8_22_1" }, { "DOI": "10.1056/NEJMoa2012410", "doi-asserted-by": "publisher", "key": "e_1_2_8_23_1" }, { "DOI": "10.1016/j.medj.2020.06.001", "doi-asserted-by": "publisher", "key": "e_1_2_8_24_1" }, { "DOI": "10.14218/JCTH.2020.00018", "doi-asserted-by": "publisher", "key": "e_1_2_8_25_1" }, { "key": "e_1_2_8_26_1", "volume-title": "LiverTox: Clinical and research information on drug‐induced liver injury [Internet]. Hydroxychloroquine", "year": "2012" } ], "reference-count": 25, "references-count": 25, "relation": {}, "resource": { "primary": { "URL": "https://onlinelibrary.wiley.com/doi/10.1002/jmv.26429" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Late onset infectious complications and safety of tocilizumab in the management of COVID‐19", "type": "journal-article", "update-policy": "https://doi.org/10.1002/crossmark_policy", "volume": "93" }

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0