{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T23:07:44Z","timestamp":1781478464717,"version":"3.54.1"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["J. Pharm. Pharm. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the potential risk of bullous pemphigoid (BP) in patients treated with immune checkpoint inhibitors (ICIs) and to characterize ICI-related BP (irBP) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The present study conducted a disproportionality analysis leveraging FAERS database, spanning the first quarter (Q1) of 2004\u20132025 Q1. To ensure robust signal detection, we employed a quadruple analytical approach incorporating: (1) reporting odds ratio (ROR), (2) proportional reporting ratio, (3) Bayesian confidence propagation neural network, and (4) multi-item gamma Poisson shrinker algorithms. These methodologies were systematically applied to assess the potential risk of BP in patients treated with ICIs. Furthermore, temporal characteristics of adverse event emergence were quantitatively assessed to delineate the time-to-onset patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There are 850 irBP cases identified, comprising reports associated with the following agents: nivolumab (n = 530), pembrolizumab (n = 180), ipilimumab (n = 44), atezolizumab (n = 40), cemiplimab (n = 24), durvalumab (n = 19), tislelizumab (n = 10), and avelumab (n = 3). Affected patients were predominantly males (67.8%) and over 60 years of age (70.1%). All eight ICIs showed positive disproportionality signals, with ROR values ranked descendingly as: cemiplimab &amp;gt; nivolumab &amp;gt; tislelizumab &amp;gt; pembrolizumab &amp;gt; ipilimumab &amp;gt; durvalumab &amp;gt; atezolizumab &amp;gt; avelumab. The median time of irBP onset was 165.2 (IQR: 56\u2013410) days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study establishes a significant link between ICIs and BP. All ICIs increase BP risk. CTLA-4 inhibitors exhibited the most marked early risk concentration, highlighting the importance of early dermatologic evaluation after initiating CTLA-4 blockade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/jpps.2025.15597","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:10:09Z","timestamp":1767766209000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Refined pharmacovigilance assessment of immune checkpoint inhibitors-related bullous pemphigoid: a multi-methodological approach utilizing FAERS database"],"prefix":"10.3389","volume":"28","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu-Yi-Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Gang","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.trecan.2023.04.002","article-title":"Immune mechanisms of toxicity from checkpoint inhibitors","volume":"9","author":"Wang","year":"2023","journal-title":"Trends Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"102556","DOI":"10.1016\/j.coi.2025.102556","article-title":"Autoimmune-related adverse events induced by immune checkpoint inhibitors","volume":"94","author":"Sun","year":"2025","journal-title":"Curr Opin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1001\/jamadermatol.2022.1624","article-title":"Association of bullous pemphigoid with immune checkpoint inhibitor therapy in patients with cancer: a systematic review","volume":"158","author":"Asdourian","year":"2022","journal-title":"JAMA Dermatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/s1470-2045(24)00278-x","article-title":"Multi-organ immune-related adverse events from immune checkpoint inhibitors and their downstream implications: a retrospective multicohort study","volume":"25","author":"Wan","year":"2024","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1001\/jamadermatol.2024.6665","article-title":"Epitope spreading in immune checkpoint inhibitor-associated bullous pemphigoid","volume":"161","author":"Koga","year":"2025","journal-title":"JAMA Dermatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1016\/j.jaad.2025.08.008","article-title":"Type 2 immunity links eczematous and lichenoid eruptions caused by immune checkpoint inhibitors","volume":"93","author":"Azin","year":"2025","journal-title":"J Am Acad Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"104808","DOI":"10.1016\/j.critrevonc.2025.104808","article-title":"T cell-mediated mechanisms of immune-related adverse events induced by immune checkpoint inhibitors","volume":"213","author":"Li","year":"2025","journal-title":"Crit Rev Oncol Hematol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1001\/jamadermatol.2021.5476","article-title":"Association of cutaneous immune-related adverse events with increased survival in patients treated with anti-programmed cell death 1 and anti-programmed cell death ligand 1 therapy","volume":"158","author":"Tang","year":"2022","journal-title":"JAMA Dermatol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/ddg.15638","article-title":"Research in practice: immune checkpoint inhibitor related autoimmune bullous dermatosis","volume":"23","author":"Pruessmann","year":"2025","journal-title":"J Dtsch Dermatol Ges"},{"key":"B10","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1001\/jamadermatol.2022.0354","article-title":"Risk factors for the development of bullous pemphigoid in US patients receiving immune checkpoint inhibitors","volume":"158","author":"Said","year":"2022","journal-title":"JAMA Dermatol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1080\/14740338.2019.1619693","article-title":"Disproportionality analysis of bullous pemphigoid adverse events with PD-1 inhibitors in the FDA adverse event reporting system","volume":"18","author":"Aggarwal","year":"2019","journal-title":"Expert Opin Drug Saf"},{"key":"B12","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/1346-8138.17517","article-title":"Immune checkpoint inhibitor-associated bullous pemphigoid: a retrospective and real-world study based on the United States food and drug administration adverse event reporting system","volume":"52","author":"Tan","year":"2025","journal-title":"J Dermatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4818","DOI":"10.1111\/jocd.14797","article-title":"Global incidence and prevalence of bullous pemphigoid: a systematic review and meta-analysis","volume":"21","author":"Lu","year":"2022","journal-title":"J Cosmet Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1001\/jamadermatol.2022.0160","article-title":"Global burden of cutaneous melanoma in 2020 and projections to 2040","volume":"158","author":"Arnold","year":"2022","journal-title":"JAMA Dermatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/s41571-023-00798-3","article-title":"Thes global burden of lung cancer: current status and future trends","volume":"20","author":"Leiter","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"79","DOI":"10.14740\/wjon1279","article-title":"Epidemiology of renal cell carcinoma","volume":"11","author":"Padala","year":"2020","journal-title":"World J Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.clinthera.2025.07.014","article-title":"Real-world utilization patterns of immune checkpoint inhibitors based on the national health insurance service data in Korea","volume":"47","author":"Kim","year":"2025","journal-title":"Clin Ther"},{"key":"B18","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/ijd.17563","article-title":"Enriched class II HLA inherence in patients with checkpoint inhibitor-associated bullous pemphigoid","volume":"64","author":"Gandarillas","year":"2025","journal-title":"Int J Dermatol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00403-024-03760-0","article-title":"Associated factors related to production of autoantibodies and dermo-epidermal separation in bullous pemphigoid","volume":"317","author":"Yang","year":"2025","journal-title":"Arch Dermatol Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1416473","DOI":"10.3389\/fimmu.2024.1416473","article-title":"The possible and intriguing relationship between bullous pemphigoid and melanoma: speculations on significance and clinical relevance","volume":"15","author":"Russo","year":"2024","journal-title":"Front Immunology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2896","DOI":"10.1016\/j.jid.2022.04.020","article-title":"Cutaneous toxicities associated with immune checkpoint inhibitors: an observational, pharmacovigilance study","volume":"142","author":"Le","year":"2022","journal-title":"J Invest Dermatol"}],"container-title":["Journal of Pharmacy &amp; Pharmaceutical Sciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontierspartnerships.org\/articles\/10.3389\/jpps.2025.15597\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:10:11Z","timestamp":1767766211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontierspartnerships.org\/articles\/10.3389\/jpps.2025.15597\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":21,"alternative-id":["10.3389\/jpps.2025.15597"],"URL":"https:\/\/doi.org\/10.3389\/jpps.2025.15597","relation":{},"ISSN":["1482-1826"],"issn-type":[{"value":"1482-1826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"article-number":"15597"}}