{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:17Z","timestamp":1792685957292,"version":"4.5.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The development of Bruton's tyrosine kinase (BTK) inhibitors has revolutionized the management of B-cell malignancies and holds potential in autoimmune diseases. However, safety concerns remain regarding treatment-associated adverse events: first-generation ibrutinib has been associated with off-target adverse event profiles, second-generation agents (acalabrutinib and zanubrutinib) require further validation of long-term safety patterns, and the real-world safety characteristics of third-generation pirtobrutinib continue to be evaluated. This study aims to characterize differences in adverse event (AE) disproportionality reporting signal patterns among four BTK inhibitors using data from the FDA Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study analyzed AE reports for four BTK inhibitors from the FAERS database via disproportionality analysis with four distinct algorithms, complemented by a clinical prioritization scoring system. Disproportionality reporting signal patterns were characterized across System Organ Class (SOC), Preferred Term (PT), and temporal distribution dimensions. A standardized 2-year observation window was applied for sensitivity analysis, and AE-mortality associations were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 77,014 AE reports were included in this study. The four BTK inhibitors showed positive disproportionality reporting signals in blood and lymphatic system disorders, cardiac disorders, and infections and infestations. However, distinct disproportionality signal patterns were observed at the PT level. Ibrutinib showed prominent cardiovascular-related disproportionality reporting signals, particularly for atrial fibrillation (ROR\u2009=\u20099.8). Acalabrutinib was characterized by a distinct headache signal. Zanubrutinib showed prominent signals for myelosuppression (ROR\u2009=\u200916.24) and haemorrhage subcutaneous (ROR\u2009=\u2009146.81). Pirtobrutinib demonstrated the strongest signal for increased white blood cell count (ROR\u2009=\u200954.28). Descriptive analysis of reported time-to-onset distributions showed that pneumonia reports for ibrutinib represented a larger proportion among cases reported after longer treatment durations, whereas haemorrhage and decreased white blood cell count reports were more frequently observed within earlier reporting intervals. In terms of fatal outcomes, multiple PTs associated with ibrutinib showed statistically significant associations with reported death outcomes within the FAERS dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This descriptive pharmacovigilance study identified distinct disproportionality reporting signal patterns for four BTK inhibitors based on FAERS data, providing potential signals for post-marketing safety surveillance. These findings should be interpreted as differences in reporting patterns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1832040","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:24:08Z","timestamp":1788495848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Generational safety profiles of BTK inhibitors: adverse reaction signals and real-world evidence from the FAERS database"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiachen","family":"Tu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Department of Pharmacy, Wuhan Huangpi District People's Hospital","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Children's Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Department of Pharmacy Administration and Clinical Pharmacy, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Children's Hospital, Capital Medical University","place":["Beijing, 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