{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:28:10Z","timestamp":1784824090465,"version":"3.55.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Comparative real-world data on the spectrum of digestive inflammatory adverse reactions across ICI classes are limited. Existing evidence on immune-related Sj\u00f6gren\u2019s syndrome\/sialadenitis consists largely of case reports and small series.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) database (2015\u20132023) to evaluate associations between ICIs and digestive inflammatory adverse reactions. Additionally, we conducted a systematic review up to July 2025 to identify published cases of ICI-associated Sj\u00f6gren\u2019s syndrome\/sialadenitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PD-1 inhibitors (pembrolizumab and nivolumab) showed the strongest associations with immune-mediated oesophagitis and gastritis. Pembrolizumab was also highly associated with hepatobiliary events, including immune-mediated cholangitis (ROR 249.18, 95% CI 169.04-367.32) and hepatitis (ROR 85.51, 95% CI 73.22-99.86). In contrast, the CTLA-4 inhibitor ipilimumab exhibited the strongest signal for immune-mediated enterocolitis. Atezolizumab and ipilimumab were significantly associated with spontaneous bacterial peritonitis. Our systematic review identified 93 cases of ICI-associated Sj\u00f6gren\u2019s syndrome\/sialadenitis, predominantly in patients with melanoma or lung cancer receiving PD-1 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PD-1 inhibitors are more strongly associated with upper GI and hepatobiliary inflammatory adverse reactions, whereas CTLA-4 inhibitors carry a higher risk of enterocolitis. These findings underscore the need for ICI-specific monitoring protocols. Early recognition and tailored management\u2014including potential treatment interruption or corticosteroid use\u2014are critical to minimizing severe outcomes. Clinicians should maintain a high index of suspicion for rare inflammatory adverse reactions such as sialadenitis, even as incidence remains low. These insights support more personalized risk-benefit assessment and inflammatory adverse reactions management in patients receiving ICIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1684475","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T06:21:54Z","timestamp":1761546114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Association between immune check point inhibitors and digestive system inflammatory adverse reactions: evidence from pharmacovigilance analysis and systematic review"],"prefix":"10.3389","volume":"16","author":[{"given":"Ya","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinchuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xirui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihao","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongju","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40425-019-0502-7","article-title":"Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury","volume":"7","author":"Abu-Sbeih","year":"2019","journal-title":"J. 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