Journal Article

DZNE-2026-01067

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tyrosine kinase inhibitor use and risk of neurodegenerative disease: A Swedish population-based cohort study.

Wittström, F. ; Chen, E. Y. ; Blotenberg, I.DZNE* ; Dahlén, T.

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71916

Abstract: Effective 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).CML 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.A 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.Initiation of nilotinib, but not imatinib or dasatinib, was associated with a significantly lower NDD incidence relative to general population comparators.

Keyword(s): Humans (MeSH) ; Sweden: epidemiology (MeSH) ; Female (MeSH) ; Neurodegenerative Diseases: epidemiology (MeSH) ; Neurodegenerative Diseases: chemically induced (MeSH) ; Male (MeSH) ; Protein Kinase Inhibitors: therapeutic use (MeSH) ; Protein Kinase Inhibitors: adverse effects (MeSH) ; Middle Aged (MeSH) ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive: drug therapy (MeSH) ; Aged (MeSH) ; Cohort Studies (MeSH) ; Pyrimidines: therapeutic use (MeSH) ; Pyrimidines: adverse effects (MeSH) ; Dasatinib: therapeutic use (MeSH) ; Dasatinib: adverse effects (MeSH) ; Imatinib Mesylate: therapeutic use (MeSH) ; Imatinib Mesylate: adverse effects (MeSH) ; Imidazoles: therapeutic use (MeSH) ; Imidazoles: adverse effects (MeSH) ; Aniline Compounds: therapeutic use (MeSH) ; Aniline Compounds: adverse effects (MeSH) ; Registries (MeSH) ; Pyrazoles: therapeutic use (MeSH) ; Pyrazoles: adverse effects (MeSH) ; Quinolines: therapeutic use (MeSH) ; Quinolines: adverse effects (MeSH) ; Tyrosine Kinase Inhibitors (MeSH) ; Proportional Hazards Models (MeSH) ; Risk Factors (MeSH) ; Nitriles (MeSH) ; Pyridazines (MeSH) ; chronic myeloid leukemia ; cohort study ; neurodegenerative disease ; pharmacoepidemiology ; tyrosine kinase inhibitors ; Protein Kinase Inhibitors ; Pyrimidines ; Dasatinib ; nilotinib ; bosutinib ; Imatinib Mesylate ; Imidazoles ; ponatinib ; Aniline Compounds ; Pyrazoles ; Quinolines ; Tyrosine Kinase Inhibitors ; Nitriles ; Pyridazines

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Contributing Institute(s):

1. Interventional Health Care Research (IHCR) (AG Thyrian)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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