Tyrosine kinase inhibitor use and risk of neurodegenerative disease: A Swedish population-based cohort study.

introductionEffective disease-modifying therapies remain unavailable for neurodegenerative diseases (NDDs). Tyrosine kinase inhibitors (TKIs) indicated for chronic myeloid leukemia (CML) have been hypothesized to modulate the pathological mechanisms underlying neurodegeneration. Therefore, we aimed to explore the association between initiation of six different TKIs and the subsequent risk of developing NDDs in Swedish nationwide registries (2005-2024).

methodsCML patients ≥50 years at diagnosis initiating TKI therapy were identified, alongside five comparators without CML matched on sex, age, and residence at diagnosis. CML cases and comparators were followed from the initiation date of the respective TKI and could contribute follow-up time to multiple TKI cohorts. A composite measure of NDD diagnosis or death due to NDD was the outcome. Hazard ratios (HRs) were estimated using Cox proportional hazards models, with adjustments for calendar year at follow-up initiation, and relevant comorbidities.

resultsA total of 1322 CML cases were included in the study. 1188 initiated imatinib (of which 41 experienced an NDD event), 541 dasatinib (15 events), 390 nilotinib (five events), 174 bosutinib, 71 ponatinib, and 41 asciminib. Adjusted hazard ratios comparing each TKI group to their matched comparator populations were 0.98 (95% confidence interval [CI], 0.71 to 1.36) for imatinib users, 1.18 (95% CI, 0.68 to 2.03) for dasatinib users, and 0.37 (95% CI, 0.15 to 0.90) for nilotinib users. Bosutinib, ponatinib, and asciminib users were too few to conduct comparative analyses. DISCUSSION: Initiation of nilotinib, but not imatinib or dasatinib, was associated with a significantly lower NDD incidence relative to general population comparators.