Adverse events associated with monoclonal antibodies used for treatment of COVID‐19: A systematic review and meta‐analysis

DOI record: { "DOI": "10.1002/bcp.70025", "ISSN": [ "0306-5251", "1365-2125" ], "URL": "http://dx.doi.org/10.1002/bcp.70025", "abstract": "<jats:sec><jats:title>Aims</jats:title><jats:p>This review aimed to synthesise the evidence related to the incidence of serious and non‐serious adverse events with the use of monoclonal antibodies (mAbs) among COVID‐19 patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Databases were searched from January 2020 to September 2023 for randomized clinical trials (RCTs) that used mAbs for the treatment of COVID‐19 regardless of disease severity. Study screening, data extraction and data analysis were performed independently by two reviewers. The Cochrane risk of bias 1.0 tool was used for methodological quality assessment.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Sixteen studies were identified for analysis with 9682 participants in the intervention arm and 10 115 participants in the control arm. Seven trials reported hepatoxicity and there was a statistically significant increase in the chance of hepatoxicity among patients treated with mAbs compared to those given standard of care (SoC) or placebo with risk ratio (RR) = 1.70, 95% confidence interval (CI) 1.29–2.24. Five trials reported for neutropenia and there was a statistically significant association of neutropenia with the use of mAbs compared to SoC or placebo with RR = 4.03, 95% CI 1.74–9.34. Ten trials reported any disease‐related serious adverse events related to the disease and there was a reduction of risk compared to SoC/placebo,  although this reduction was not statistically significant (RR = 0.88, 95% CI 0.70–1.11).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The use of mAbs was found to be associated with an increased risk of hepatoxicity and neutropenia compared to SoC/placebo among COVID‐19 patients with moderate certainty of evidence. Long‐term observational studies are recommended to observe post‐COVID adverse events related to the use of mAbs.</jats:p></jats:sec>", "alternative-id": [ "10.1002/bcp.70025" ], "author": [ { "ORCID": "https://orcid.org/0000-0003-2143-8629", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Htet", "given": "Htet", "sequence": "first" }, { "ORCID": "https://orcid.org/0009-0005-8428-6177", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Kyung", "given": "Han You", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0326-424X", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Burud", "given": "Ismail Abdul Sattar", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-9948-4428", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Jaiprakash", "given": "Heethal", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-7073-8092", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Subramaniam", "given": "Thiruselvi", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-2852-8486", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Iezhitsa", "given": "Igor", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-3050-7449", "affiliation": [ { "name": "School of Medicine IMU University Kuala Lumpur Malaysia" } ], "authenticated-orcid": false, "family": "Agarwal", "given": "Renu", "sequence": "additional" } ], "container-title": "British Journal of Clinical Pharmacology", "container-title-short": "Brit J Clinical Pharma", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 3, 10 ] ], "date-time": "2025-03-10T06:51:32Z", "timestamp": 1741589492000 }, "deposited": { "date-parts": [ [ 2025, 4, 28 ] ], "date-time": "2025-04-28T07:16:31Z", "timestamp": 1745824591000 }, "funder": [ { "DOI": "10.13039/501100009381", "award": [ "BMS I‐2022 (15)" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100009381", "id-type": "DOI" } ], "name": "International Medical University" } ], "indexed": { "date-parts": [ [ 2025, 4, 29 ] ], "date-time": "2025-04-29T04:01:16Z", "timestamp": 1745899276904, "version": "3.40.4" }, "is-referenced-by-count": 1, "issue": "5", "issued": { "date-parts": [ [ 2025, 3, 6 ] ] }, "journal-issue": { "issue": "5", "published-print": { "date-parts": [ [ 2025, 5 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by-nc/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 3, 6 ] ], "date-time": "2025-03-06T00:00:00Z", "timestamp": 1741219200000 } } ], "link": [ { "URL": "https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1002/bcp.70025", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "311", "original-title": [], "page": "1306-1321", "prefix": "10.1002", "published": { "date-parts": [ [ 2025, 3, 6 ] ] }, "published-online": { "date-parts": [ [ 2025, 3, 6 ] ] }, "published-print": { "date-parts": [ [ 2025, 5 ] ] }, "publisher": "Wiley", "reference": [ { "article-title": "COVID‐19 pandemic: from origins to outcomes. 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PubMed", "year": "2012" }, { "DOI": "10.1016/j.jbspin.2022.105510", "doi-asserted-by": "publisher", "key": "e_1_2_10_55_1" }, { "DOI": "10.1111/eci.12799", "doi-asserted-by": "publisher", "key": "e_1_2_10_56_1" }, { "DOI": "10.1101/2020.02.03.931766", "doi-asserted-by": "publisher", "key": "e_1_2_10_57_1" }, { "DOI": "10.1177/1756284820959183", "doi-asserted-by": "publisher", "key": "e_1_2_10_58_1" }, { "DOI": "10.1111/aas.13795", "doi-asserted-by": "publisher", "key": "e_1_2_10_59_1" }, { "DOI": "10.1186/s13063‐021‐05963‐6", "doi-asserted-by": "publisher", "key": "e_1_2_10_60_1" }, { "DOI": "10.1177/0192623312467400", "doi-asserted-by": "publisher", "key": "e_1_2_10_61_1" }, { "DOI": "10.1371/journal.pone.0269368", "doi-asserted-by": "publisher", "key": "e_1_2_10_62_1" }, { "DOI": "10.1007/s12026‐014‐8590‐4", "doi-asserted-by": "publisher", "key": "e_1_2_10_63_1" }, { "DOI": "10.3109/s10165‐010‐0279‐5", "doi-asserted-by": "publisher", "key": "e_1_2_10_64_1" }, { "DOI": "10.1111/aas.13795", "doi-asserted-by": "publisher", "key": "e_1_2_10_65_1" }, { "article-title": "Retrospective analysis of tocilizumab‐induced neutropenia in patients with rheumatoid arthritis [abstract]", "author": "Kim Y", "issue": "9", "journal-title": "Arthritis Rheumatol", "key": "e_1_2_10_66_1", "volume": "74", "year": "2022" }, { "DOI": "10.1093/rheumatology/keq343", "doi-asserted-by": "publisher", "key": "e_1_2_10_67_1" }, { "DOI": "10.1136/annrheumdis‐2013–203559", "doi-asserted-by": "publisher", "key": "e_1_2_10_68_1" }, { "DOI": "10.18176/jiaci.0314", "doi-asserted-by": "publisher", "key": "e_1_2_10_69_1" }, { "key": "e_1_2_10_70_1", "unstructured": "Actemra (tocilizumab)—risk of fatal anaphylaxis—for health professionals: health Canada endorsed important safety information on Actemra (tocilizumab).http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2010/14586a-eng.php" }, { "DOI": "10.1136/annrheumdis‐2016–210297", "doi-asserted-by": "publisher", "key": "e_1_2_10_71_1" }, { "DOI": "10.1093/rheumatology/keu181", "doi-asserted-by": "publisher", "key": "e_1_2_10_72_1" }, { "DOI": "10.1136/ard.2011.151092", "doi-asserted-by": "publisher", "key": "e_1_2_10_73_1" }, { "DOI": "10.1136/annrheumdis‐2014–206695", "doi-asserted-by": "publisher", "key": "e_1_2_10_74_1" }, { "DOI": "10.5414/CN109971", "doi-asserted-by": "publisher", "key": "e_1_2_10_75_1" }, { "DOI": "10.3390/medicina59091517", "doi-asserted-by": "publisher", "key": "e_1_2_10_76_1" }, { "DOI": "10.1080/0886022X.2023.2268213", "doi-asserted-by": "publisher", "key": "e_1_2_10_77_1" }, { "DOI": "10.1101/2022.04.20.22274090", "doi-asserted-by": "publisher", "key": "e_1_2_10_78_1" }, { "DOI": "10.1016/j.cmi.2020.10.036", "doi-asserted-by": "publisher", "key": "e_1_2_10_79_1" }, { "DOI": "10.18632/aging.203834", "doi-asserted-by": "publisher", "key": "e_1_2_10_80_1" }, { "DOI": "10.1016/j.cmi.2022.05.005", "doi-asserted-by": "publisher", "key": "e_1_2_10_81_1" } ], "reference-count": 80, "references-count": 80, "relation": {}, "resource": { "primary": { "URL": "https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/bcp.70025" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Adverse events associated with monoclonal antibodies used for treatment of COVID‐19: A systematic review and meta‐analysis", "type": "journal-article", "volume": "91" }