{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:49:56Z","timestamp":1788572996431,"version":"build-2803163510"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"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>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) are associated with rare but life-threatening immune-related adverse events. Myocarditis\u2013myositis\u2013myasthenia gravis (MMM) overlap is among the most severe neuromuscular\u2013cardiac toxicity patterns, but population-scale data on disproportionality, reported death outcomes, and time-to-onset (TTO) remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) from 2015Q1 to 2025Q4. Strict MMM overlap was defined at the report level by co-reporting of the Preferred Terms \u201cmyocarditis,\u201d \u201cmyositis,\u201d and \u201cmyasthenia gravis\u201d. ICI exposure was restricted to selected PD-1, PD-L1, and CTLA-4 inhibitors recorded as primary or secondary suspect drugs (PS\/SS), with a prespecified sensitivity analysis restricted to PS reports only. Disproportionality was assessed primarily using reporting odds ratios (RORs) with Haldane\u2013Anscombe correction for sparse cells; the Information Component (IC) and IC025 were calculated as complementary Bayesian metrics. Drug-level TTO was estimated by linking therapy start dates and event dates within eligible reports.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 15,187,311 deduplicated FAERS reports, 151 met the strict MMM overlap definition, including 131 ICI-exposed reports. ICI exposure showed a strong disproportionality signal for strict MMM overlap (ROR 397.29, 95% CI 249.44\u2013632.76; IC 5.50, IC025 5.24). Reported death outcomes were observed in 49\/131 (37.4%) ICI-exposed MMM overlap reports, including 31\/80 (38.8%) in PD-1 reports, 5\/16 (31.3%) in PD-L1 reports, and 13\/35 (37.1%) in combination ICI reports. Drug-level TTO was available for 53 ICI-exposed reports, with a median of 25 days (IQR 18\u201338); restricting to TTO \u2264365 days yielded a similar median of 24 days (IQR 18\u201337), supporting a predominantly early-onset pattern. Sensitivity analyses restricted to PS were directionally consistent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In FAERS, ICI-associated strict MMM overlap showed a strong disproportionality signal and predominantly early reported onset; reported death outcomes were also observed in a substantial proportion of ICI-exposed overlap reports. These findings support heightened clinical vigilance for cardio-neuromuscular overlap toxicity, particularly during the first months after ICI initiation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1825269","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T04:17:17Z","timestamp":1779077837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Immune checkpoint inhibitors and myocarditis\u2013myositis\u2013myasthenia gravis overlap: a FAERS pharmacovigilance study with time-to-onset characterization"],"prefix":"10.3389","volume":"17","author":[{"given":"Burak","family":"Pacaci","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Alperen","family":"Tunc","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Demirel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firat","family":"Akagunduz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkam","family":"Kocaaslan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Kaan","family":"Guren","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazim Can","family":"Demircan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Vedat","family":"Bayoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Marmara University Pendik Training and Research Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101950","DOI":"10.1016\/j.gore.2025.101950","article-title":"Adverse events beyond the RUBY trial: reporting immunotherapy-associated myocarditis, myositis, and myasthenia gravis in a real-world endometrial cancer case","volume":"61","author":"Abozenah","year":"2025","journal-title":"Gynecol. 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