{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:39:49Z","timestamp":1787585989713,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["22K12890"],"award-info":[{"award-number":["22K12890"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: One type of immune-related adverse event caused by immune checkpoint inhibitors (ICIs) is pituitary-related adverse events. The management of pituitary-related adverse events is important because they can be fatal if not treated promptly. Therefore, this study was conducted to investigate the onset of pituitary-related adverse events using the Japanese Adverse Drug Report (JADER) database. Materials and Methods: Cases registered in the JADER database from 2004 to 2019 were used. The target drugs were ipilimumab, nivolumab, pembrolizumab, avelumab, atezolizumab, and durvalumab, and the target adverse events were the high-level terms \u201cAnterior pituitary hypofunction,\u201d \u201cAnterior pituitary hyperfunction,\u201d \u201cPosterior pituitary disorder,\u201d and \u201cPituitary neoplasm\u201d in the Medical Dictionary for Regulatory Activities, Japanese version (MedDRA\/J). The information component (IC) was used for signal detection and IC delta (IC\u0394) was used for women-related signals. Onset timing and patterns were analyzed using the Weibull distribution. Results: Signals were detected with ipilimumab, nivolumab, pembrolizumab, and atezolizumab in \u201cAnterior pituitary hypofunction,\u201d with ICs and 95% credible intervals (95%CrI) of 5.53 (5.30\u20135.69), 4.96 (4.79\u20135.08), 4.04 (3.76\u20134.25), and 2.40 (1.53\u20133.00). Significant signals were detected in women, except for atezolizumab. Additionally, the time of onset was classified as the wear-out failure type. Inverse signals were detected with ipilimumab and nivolumab in \u201cPosterior pituitary disorder,\u201d with ICs (95%CrI) of \u22121.24 (\u22122.80\u2013\u22120.26), and \u22120.89 (\u22121.64\u2013\u22120.37). Conclusions: Anterior pituitary hypofunction is likely to occur with the long-term administration of ipilimumab, nivolumab, and pembrolizumab. Further investigation is needed to determine the differences in the tendencies to detect signals in the anterior and posterior pituitaries between ipilimumab and nivolumab.<\/jats:p>","DOI":"10.3390\/medicina59111963","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:23:39Z","timestamp":1699356219000},"page":"1963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pituitary-Related Adverse Events and Onset Patterns Caused by Immune Checkpoint Inhibitors: Analysis Using the Japanese Adverse Drug Event Report Database"],"prefix":"10.3390","volume":"59","author":[{"given":"Hiroki","family":"Asano","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki-shi 503-8502, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-9604","authenticated-orcid":false,"given":"Yoshihiro","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu-shi 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki-shi 503-8502, Gifu, Japan"},{"name":"Laboratory of Clinical Pharmacy, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu-shi 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiseki","family":"Usami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki-shi 503-8502, Gifu, Japan"},{"name":"Laboratory of Clinical Pharmacy, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu-shi 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu-shi 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e007557","DOI":"10.1136\/jitc-2023-007557","article-title":"Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events","volume":"11","author":"Gente","year":"2023","journal-title":"J. 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