| アブストラクト | BACKGROUND: Broad pharmacovigilance profiles of Bruton tyrosine kinase (BTK) inhibitors have been described, but respiratory adverse events have not been systematically characterized across individual agents using independent reporting systems. We therefore focused on respiratory reporting phenotypes and their cross-database reproducibility. METHODS: We analyzed spontaneous reports involving ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib in FAERS and JADER. Preferred terms (PTs) within the MedDRA Respiratory, thoracic and mediastinal disorders system organ class were screened using the reporting odds ratio (ROR), which was prespecified as the primary disproportionality measure. A signal required at least three reports and a lower 95% confidence limit of the ROR >1. Cross-database replication required the same drug-PT combination to meet this criterion independently in both databases. Pneumonia was evaluated separately because it is formally classified under Infections and infestations. For pneumonia, PRR, BCPNN, and MGPS were added as supportive sensitivity analyses to assess signal robustness without altering the primary ROR classification. Time to onset was characterized using exact treatment-start and event-onset dates and Weibull models when sufficient data were available. RESULTS: FAERS contained 84,217 target-drug reports and 255,010 adverse-event records, whereas JADER contained 1,368 reports and 2,035 adverse-event records. Within the respiratory SOC, 70 drug-PT combinations met the ROR criterion in FAERS and five in JADER. Three signals were replicated across databases, all involving ibrutinib: epistaxis, haemothorax, and pleural effusion. Pneumonia met the primary ROR criterion for all four agents in FAERS and for ibrutinib, acalabrutinib, and pirtobrutinib in JADER. Multi-algorithm agreement supported the robustness of the pneumonia signal for ibrutinib and pirtobrutinib in FAERS and for ibrutinib, acalabrutinib, and pirtobrutinib in JADER. In FAERS, pneumonia showed early-failure Weibull patterns for ibrutinib (beta=0.55, 95% CI 0.53-0.58) and acalabrutinib (beta=0.69, 95% CI 0.59-0.83); corresponding JADER estimates were compatible with random-failure patterns. CONCLUSIONS: Respiratory reporting patterns varied across BTK inhibitors and were only partly reproducible across FAERS and JADER. Cross-database replication was concentrated in selected ibrutinib-associated respiratory events, whereas pneumonia showed reproducible ROR signals for three agents. These findings characterize reporting patterns rather than incidence or comparative clinical risk. |
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