Use of receptor and nonreceptor tyrosine kinase inhibitors and Parkinson disease risk.
Use of receptor and nonreceptor tyrosine kinase inhibitors and Parkinson disease risk.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Phoenix, US · Author affiliation
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.Location evidence
St. Louis, US · Author affiliation
Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA; Center for Advancing Health Services, Policy & Economics Research, Washington University, St. Louis, Missouri, USA.Location evidence
Johannesburg, ZA · Author affiliation
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA; Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA; School of Public Health, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: Brad.Racette@Barrowneuro.org.Location evidence
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Original abstract
There are currently no disease-modifying therapies for Parkinson disease (PD), although various targets for disease modification have been explored. Expression and binding of receptor tyrosine kinases (rTKs) and nonreceptor tyrosine kinases (nrTKs) have been implicated in PD pathogenesis, and their inhibition is a promisingneuroprotective strategy. This population-based, case-control study of US Medicare beneficiaries included 207,532 incident PD patients and 975,177 comparable, population-based control subjects from 2016 to 2018. This study investigated associations between Medicare Part D prescription fills prior to PD diagnosis for 7 rTK inhibitors (erlotinib, sorafenib, pazopanib, imatinib, sunitinib, nintedanib, and dasatinib) and 4 nrTK inhibitors (nilotinib, ibrutinib, ruxolitinib, and tofacitinib) and PD risk. Logistic regression estimated relative risks (RR) and 95% confidence intervals (CIs) adjusted for age, sex, race, smoking, and healthcare utilization. All medications were inversely associated with incident PD. The rTK inhibitors erlotinib (RR = 0.53, 95% CI: 0.38-0.74), sorafenib (RR = 0.43, 95% CI: 0.25-0.74), imatinib (RR = 0.60, 95% CI: 0.47-0.75), pazopanib (RR = 0.58, 95% CI: 0.39-0.86), nintedanib (RR = 0.66, 95% CI: 0.50-0.88), sunitinib (RR = 0.60, 95% CI: 0.39-0.93), and dasatinib (RR = 0.53, 95% CI: 0.35-0.82) had the strongest inverse associations. Among nrTK inhibitors, ibrutinib (RR = 0.62, 95% CI: 0.51-0.75) had a marked inverse association. Given the chemotherapeutic mechanisms of these medications, and the known cancer-PD inverse relationship, we performed a sensitivity analysis adjusting for relevant cancer subtypes, yielding a similar inverse association. Overall, the use of rTK and nrTK inhibitors was associated with a lower risk of developing PD, although there may be differential impact of this medication class depending on specific inhibition pathways.