Age-Stratified Disproportionality Analysis of Bruton's tyrosine kinase inhibitors in FAERS and VigiBase

INTRODUCTION: Bruton's Tyrosine Kinase inhibitors (BTKis) are increasingly used because of their efficacy; however, safety concerns are emerging. METHODS: This study extracted data from FAERS and VigiBase and divided patients into four age groups. The Reporting Odds Ratio (ROR) was used to identify safety signals. RESULTS: Regarding cardiac disorders, zanubrutinib showed a specific cardiac arrest signal in the 0-60-year age group in FAERS, and the Atrial Fibrillation (AF) signal intensity increased with age in VigiBase. Conversely, the AF signals decreased across successive age groups for acalabrutinib in VigiBase and for ibrutinib in both databases. Several cardiac PTs for acalabrutinib met the signal criteria in the 61-70-year group. For skin and subcutaneous tissue disorders, multiple nail-related Adverse Drug Events (ADEs) were observed in all age groups for ibrutinib; acalabrutinib and zanubrutinib exhibited no nail-related signals, whereas other skin-related signals were primarily detected in patients aged >60 years. Regarding bleeding ADEs, thirty types were detected for ibrutinib and four for acalabrutinib; zanubrutinib showed no age-specific bleeding signals. For infections and infestations, among the PTs detected in three or more age groups, aspergillus infection, bronchopulmonary aspergillosis, and onychomycosis were consistently ranked among the top ten signals for ibrutinib based on VigiBase ROR025 across all four age groups, with ROR025 values decreasing with increasing age. Signals for different types of pneumonia were detected in all age groups for the BTKis, except in the 0-60- year age group of zanubrutinib. Moreover, the specific signals warrant further attention. DISCUSSION: This comprehensive analysis of FAERS and VigiBase data highlights age-related differences in ADE reporting across BTKi therapies. These findings identify age-stratified reporting patterns that may help prioritize further safety investigations. A limitation of this study is the lack of integration of potential biological mechanisms underlying BTKi-related ADEs. CONCLUSION: This study identified age-stratified reporting patterns for three BTKis in two spontaneous reporting systems. These findings are hypothesis-generating and do not establish differences in clinical risk across age groups or causal relationships.