{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:26:32Z","timestamp":1792110392553,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Immune\u2010checkpoint inhibitors (ICI) have revolutionized cancer treatment but are responsible for various immune\u2010related adverse events (irAE). The impact of non\u2010anticancer medications (comedications) on irAE occurrence remains largely unexplored. The objective of this study was to assess comedications associated with an increased reporting of irAE with ICIs. In this pharmacovigilance study, all individual case safety reports (ICSRs) involving ICIs reported in the World Health Organization international pharmacovigilance database Vigibase up to January 2024 were extracted. All suspect or interacting comedications were analyzed individually and as drug classes using Anatomical Therapeutic Chemical classification level 4. The primary outcome was the reporting odds ratio (ROR) of irAE in patients who received both an ICI and the comedication of interest, compared with ICI\u2010treated patients who did not receive that comedication. Among 169,753 ICSRs involving an ICI, a total of 314,366 comedications were recorded, with 8,122 identified as \u201csuspect or interacting.\u201d Analysis shows an increased reporting of nephritis with proton pump inhibitors (PPI) (ROR\u2009=\u200929.62 [95% CI\u2009=\u200918.61\u201347.14]) and with non\u2010steroidal anti\u2010inflammatory drugs (ROR\u2009=\u200910.47 [95% CI\u2009=\u20094.15\u201326.41]), myositis with statins (ROR\u2009=\u20099.41 [95% CI\u2009=\u20093.50\u201325.30]), ketoconazole with hepatitis (ROR\u2009=\u200920.49 [95% CI\u2009=\u20091.53\u2013274.17]) and autoimmune bullous disease with dipeptyl\u2010peptidase\u20104 inhibitors (ROR\u2009=\u200946.42 [95% CI\u2009=\u200911.71\u2013184.05]), among others. Various drugs, including PPI (ROR\u2009=\u20098.61 [95% CI\u2009=\u20093.48\u201321.26]), some anti\u2010infectives (sulfamethoxazole, ROR\u2009=\u200931.31 [95% CI\u2009=\u200913.32\u201373.61], clavulanic acid, ROR\u2009=\u200918.12 [95% CI\u2009=\u20094.77\u201368.89]), allopurinol (ROR\u2009=\u200957.11 [95% CI\u2009=\u200911.27\u2013289.39]) or levetiracetam (ROR\u2009=\u200914.91 [95% CI\u2009=\u20092.15\u2013103.64]) were associated with serious cutaneous adverse reactions. Complementary analysis showed higher ROR in the ICI population versus without ICI for the association of nephritis with ibuprofen (ROR<jats:sub>ICI<\/jats:sub>\u2009=\u200927.82 <jats:italic>vs.<\/jats:italic> ROR<jats:sub>VigiBaseWithoutICI<\/jats:sub>\u2009=\u20093.56, ROR<jats:sub>ratio<\/jats:sub>\u2009=\u20097.81 [95% CI\u2009=\u20091.23\u201349.50]) and myocarditis with influenza vaccine (ROR<jats:sub>ICI<\/jats:sub>\u2009=\u200922.74 vs. ROR<jats:sub>VigiBaseWithoutICI<\/jats:sub>\u2009=\u20090.66, ROR<jats:sub>ratio<\/jats:sub>\u2009=\u200934.45 [95% CI\u2009=\u20091.66\u2013723.24]), suggesting a synergistic toxicity. This study identified multiple comedications associated with an increased reporting of specific irAE. Some of them might be synergistic warranting further investigation.<\/jats:p>","DOI":"10.1002\/cpt.3721","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:10:33Z","timestamp":1751191833000},"page":"593-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comedications Associated with Immune\u2010Related Adverse Events from Immune\u2010Checkpoint Inhibitors"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3631-5408","authenticated-orcid":false,"given":"L\u00e9onard","family":"Laurent","sequence":"first","affiliation":[{"name":"Residual Tumor &amp; Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer Institut Curie, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-8131","authenticated-orcid":false,"given":"Baptiste","family":"Abbar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2010 H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Centre d'Immunologie et des Maladies Infectieuses (CIMI\u2010Paris), Inserm U1135 Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-0237","authenticated-orcid":false,"given":"Kevin","family":"Bihan","sequence":"additional","affiliation":[{"name":"Department of PharmacologyInstitut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Assistance Publique \u2010 H\u00f4pitaux de Paris (AP\u2010HP), Clinical Investigation Center (CIC\u20101901), Regional Pharmacovigilance Centre Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-719X","authenticated-orcid":false,"given":"Elise","family":"Dumas","sequence":"additional","affiliation":[{"name":"Residual Tumor &amp; Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer Institut Curie, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Mathematics \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-3936","authenticated-orcid":false,"given":"Floriane","family":"Jochum","sequence":"additional","affiliation":[{"name":"Residual Tumor &amp; Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer Institut Curie, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Gynecology Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Lebrun\u2010Vignes","sequence":"additional","affiliation":[{"name":"Department of PharmacologyInstitut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Assistance Publique \u2010 H\u00f4pitaux de Paris (AP\u2010HP), Clinical Investigation Center (CIC\u20101901), Regional Pharmacovigilance Centre Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-2479","authenticated-orcid":false,"given":"Jean\u2010Philippe","family":"Spano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2010 H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0331-3307","authenticated-orcid":false,"given":"Joe\u2010Elie","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of PharmacologyInstitut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Assistance Publique \u2010 H\u00f4pitaux de Paris (AP\u2010HP), Clinical Investigation Center (CIC\u20101901), Regional Pharmacovigilance Centre Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4430-3022","authenticated-orcid":false,"given":"Anne\u2010Sophie","family":"Hamy","sequence":"additional","affiliation":[{"name":"Residual Tumor &amp; 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