(A-224) Signal Detection of Dementia Associated with Alkylating Agents: Using the World Health Organization Pharmacovigilance Database

Background: Alkylating agents are crucial in cancer treatment, but their cognitive side effects, like dementia, are understudied.

Objectives: To assess the association between alkylating agents and dementia by performing a disproportionality analysis using World Health Organizations' VigiBase database.

Methods: We performed a disproportionality analysis using VigiBase data from January 1, 2000 to December 31, 2024, encompassing more than 16 million suspected adverse drug reaction reports from 131 national pharmacovigilance authorities worldwide. Alkylating agent drugs in our study included Nitrogen mustards, Nitrosoureas, Alkyl sulfonates, Triazines, and Ethylenimides. Dementia events were identified using Preferred Term (PT) codes and standardized MedDRA Queries (SMQ).
We excluded any ICSRs that lacked essential details. Such as reports were excluded if they had incomplete data, an unknown or non-parenteral route of administration, missing or unreported sex information, or no preferred term code. In addition, only ICSRs where drug involvement was reported as suspected were retained to enhance data validity. We examined statistical signals using Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC). A signal detection methodology was applied to evaluate the frequency of dementia reports relative to all other adverse events, with criteria for a significant signal defined as a PRR exceeding 2 with a chi-square value of at least 4, an elevated ROR, and a positive lower limit of the 95% confidence interval for the IC.

Results: A total number of ICSRs in our analysis was approximately 43.18 million. Among these, 9,267,146 (approximately 21.4%) were from patients aged 65 years and older. The PRR was 1.75, the ROR was 1.70 (95% CI: 0.95–3.05), and the IC was 0.55. However, in the subgroup of patients aged 65 and older, a significant signal was observed, with an IC value of 1.05.

Conclusions: Our findings indicate that the overall does not demonstrate a statistically significant signal for dementia associated with alkylating agents, a distinct and significant signal emerges in patients aged 65 and older (IC value of 1.05). This age-dependent pattern suggests that elderly patients may exhibit heightened vulnerability to neurocognitive effects from these agents, meriting further investigation into tailored monitoring and underlying mechanisms.