Table 1_Peripheral and central nervous system toxicities of Bruton tyrosine kinase Inhibitors: a real-world pharmacovigilance study.docx

Disproportionality analyses were performed using reporting odds ratio (ROR) and proportional reporting ratio (PRR), and multivariate logistic regression was applied to adjust for confounders, including age, sex, and weight. Time-to-onset distributions, severity patterns, and mortality rates were also evaluated.</p>Results<p>Out of 75,240 BTK inhibitor-associated AE reports, 10,435 (13.87%) were coded to the MedDRA System Organ Class (SOC) “Nervous system disorders.” Ibrutinib contributed the largest absolute number of neurological AE reports (n = 9,097), followed by acalabrutinib (n = 1,129) and zanubrutinib (n = 209).

The most frequently reported events included headache, dizziness, cerebrovascular accident, loss of consciousness, and peripheral neuropathy. At the SOC level, however, no overall positive disproportionality signal was observed for any of the three agents (acalabrutinib ROR = 0.95, 95% CI 0.90–1.01; ibrutinib ROR = 0.68, 95% CI 0.67–0.69; zanubrutinib ROR = 0.61, 95% CI 0.54–0.69). Positive signals were instead identified for selected preferred terms, including clinically important haemorrhagic and cerebrovascular events.

Reported fatal outcomes were most frequent among reports containing cerebrovascular accident and cerebral hemorrhage; these findings should be interpreted cautiously because FAERS does not adjudicate cause of death.</p>Conclusion<p>In this FAERS-based pharmacovigilance study, BTK inhibitors showed distinct reporting patterns of nervous system disorders AEs, particularly at the preferred-term and HLGT levels, rather than an overall SOC-level disproportionality signal.

Ibrutinib contributed the largest number of neurological AE reports, whereas comparisons involving zanubrutinib require caution because of sparse reporting and shorter market exposure. These findings support careful neurological monitoring and individualized risk assessment, but they should not be interpreted as evidence of causality.</p>