Abstract Details

Title Use of Receptor and Non-receptor Tyrosine Kinase Inhibitors Is Associated with Lower Risk of Developing Parkinson Disease

Topic Movement Disorders

Presentation(s) S35 - Movement Disorders: Hyperkinetic Movement Disorders (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Background

Currently, no disease-modifying therapies exist for PD. Receptor and non-receptor tyrosine kinases such as Abelson tyrosine kinase (ABL) are implicated in PD pathogenesis via their induction of neuroinflammation, α-synuclein phosphorylation/aggregation, and mitochondrial dysfunction resulting in neuronal toxicity and death. Although a randomized controlled trial of the ABL inhibitor nilotinib failed to demonstrate evidence of disease modification, other rTK/nrTK inhibitors may still be promising as neuroprotective therapies.

Objective To test the association between the use of receptor tyrosine kinase inhibitors (rTKI)/non-receptor tyrosine kinase inhibitors (nrTKI) and Parkinson disease (PD) risk.

Design/Methods Using U.S. Medicare data, we conducted a population-based, case-control study of 200,437 incident PD patients and 941,727 comparable, population-based controls diagnosed/selected in 2016-2018. We tested the association between Part D prescription fills in the prior 2-5 years for seven rTKIs (Erlotinib, Imatinib, Nilotinib, Nintedanib, Pazopanib, Sorafenib, Sunitinib) and four nrTKIs (Dasatinib, Ibrutinib, Ruxolitinib, and Tofacitinib) and PD risk. We used logistic regression to estimate relative risks (RR) and 95% confidence intervals (CI), and to adjust for demographics, smoking, and healthcare utilization.

Results All 11 TK inhibitors were inversely-associated with PD. Beneficiaries taking tyrosine kinase inhibitors targeting ERBb (Erlotinib, RR 0.51, CI 0.35-0.74), TEC (Ibrutinib, RR 0.60, CI 0.49-0.74), or PDGF, VEGF, FGFR, and/or SRC, i.e. Sorafenib (RR 0.48, CI 0.27-0.84), Imatinib (RR 0.59, CI 0.46-0.75), Pazopanib (RR 0.58, CI 0.39-0.88), Nintedanib (RR 0.67, CI 0.50-0.90), Sunitinib (RR 0.64, CI 0.41-1.00), and Dasatinib (RR 0.54, CI 0.35-0.83) tended to have the most marked inverse associations. The nrTKIs inhibiting JAK, i.e., Ruxolitinib (RR 0.81, CI 0.60-1.10) and Tofacitinib (RR 0.88, CI 0.68-1.14), exhibited more modest inverse associations, as did the ABL/PDGF inhibitor Nilotinib (RR 0.71, CI 0.47-1.09).

Conclusions rTKIs and nrTKIs might reduce risk of developing PD and there may be some differential impact of this class of medications depending on specific inhibition pathways and indication.

Authors/Disclosures
Giovanni R. Malaty, MD (Barrow Neurological Institute) PRESENTER	Dr. Malaty has nothing to disclose.
Susan Nielsen (Washington University in St. Louis)	No disclosure on file
Osvaldo J. Laurido-Soto, MD (Washington University)	The institution of Dr. Laurido-Soto has received research support from Washington University in St. Louis.
Brad A. Racette, MD, FAAN (Barrow Neurological Institute)	Dr. Racette has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for American Regent. Dr. Racette has received personal compensation in the range of $500-$4,999 for serving as a advisory council with NIEHS.