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Novel therapies that target the inflammatory mechanisms driving acute exacerbations of COPD are required. The ST2 receptor, which binds the alarmin interleukin (IL)-33 to initiate an inflammatory response, is a potential target. Astegolimab, a fully human immunoglobulin G2 monoclonal antibody, which binds with high affinity to ST2 to prevent binding of IL-33, is a potential therapy for COPD. However, targeting inflammatory pathways that form part of the immune system may have unintended consequences, such as implications for the response to infection and cardiovascular function. Therefore, an understanding of astegolimab\u2019s safety profile in clinical use is essential. This narrative review summarizes clinical safety data from published clinical trials of astegolimab with a focus on adverse events of interest, including infections and cardiac events. Astegolimab was shown to be well tolerated in &gt;\u2009580 patients with asthma, atopic dermatitis, COPD, and severe COVID-19 pneumonia who took part in Phase II trials. The frequency of adverse events (AEs) and serious AEs was similar between the astegolimab and placebo arms in each trial (AEs: 41\u201381% vs. 58\u201377%; serious AEs: 3\u201329% vs. 0\u201341%, respectively). The number of deaths was similar between treatment arms and there were no astegolimab-related deaths. Astegolimab did not increase the risk of infection or major adverse cardiac events. Ongoing Phase IIb and Phase III trials of astegolimab in patients with COPD who have a history of frequent acute exacerbation(s) of COPD will provide a future opportunity to confirm the safety profile of astegolimab.<\/jats:p>","DOI":"10.1186\/s12931-025-03360-0","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:49:21Z","timestamp":1761742161000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safety and tolerability of astegolimab, an anti-ST2 monoclonal antibody: a narrative review"],"prefix":"10.1186","volume":"26","author":[{"given":"Steven G.","family":"Kelsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Dash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Fong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Theess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Alvaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"3360_CR1","doi-asserted-by":"crossref","unstructured":"Maspero J, Adir Y, Al-Ahmad M, et al. 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Ethics Committees for each site approved the protocols in each study. The COPD-ST2OP trial was performed in accordance with the principles of the Declaration of Helsinki and ethics approval given by East Midlands \u2013 Leicester South Research Ethics Committee. In all trials, patients (or their legally authorized representatives) provided written, informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SGK has received funding from Genentech Inc., Syneos, and Teva. MM was recently a speaker and\/or advisor for and\/or had received research funding from Alexion, Allakos, Almirall, Alvotech, Amgen, Aquestive Therapeutics, Arcensus, argenX, AstraZeneca, Astria Therapeutics, BioCryst Pharmaceuticals, Blueprint Medicines, Celldex Therapeutics, Celltrion, Clinuvel, Cogent Biosciences, CSL Behring, Escient Pharmaceuticals, Evommune, Excellergy Therapeutics, Genentech, Inc., GSK, Incyte, Jasper Therapeutics, KalVista Pharmaceuticals, Kashiv Biosciences, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Mitsubishi Tanabe Pharma, Moxie, Noucor, Novartis, Orion Biotechnology, Pharvaris, Resonance Medicine, Sanofi\/Regeneron, Santa Ana Bio, Septerna, Servier, Takeda, Teva, Third Harmonic Bio, ValenzaBio, Vitalli Bio, Yuhan Corporation, and Zura Bio. MW has no competing interests to declare. GA and WT are employees of F. Hoffmann-La Roche, Ltd. AD, AF, and XY are employees of Genentech, Inc. DM is an employee of Genentech, Inc. and a shareholder of F. Hoffmann-La Roche, Ltd.\/Genentech, Inc. CEB has received grants and consultancy fees from 4D Pharma, Areteia, AstraZeneca, Chiesi, F. Hoffmann-La Roche, Ltd., Genentech, Inc., GlaxoSmithKline, Mologic, Novartis, Regeneron Pharmaceuticals, and Sanofi paid to his institution.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"302"}}