2024 American Academy of Neurology Abstract Website

Objective:

To investigate the role of immunosuppressants in Parkinson Disease (PD) risk.

Background:

PD is the second most common neurodegenerative disease, for which finding a neuroprotective therapy that can slow or halt progression is crucial. PD is likely multiple diseases with a common, but variable, phenotype. Nevertheless, neuroinflammation may represent a common neurodegenerative pathway and medications that target inflammation are potential disease-modifying therapies. Identifying agents with neuroprotective effects in PD has been challenging.

Design/Methods:

We conducted a population-based case-control study using Medicare claims data from the United States. The study included 200,437 incident PD cases and 941,727 controls from 2016-2018 and without Lewy body dementia or atypical parkinsonism. We tested the association between PD risk and immunosuppressant use during the prodromal disease period. We identified 47 immunosuppressants, representing 9 unique medication classes, in Part D prescription claims data in the 2-5 years prior to PD diagnosis/control selection. We used logistic regression to estimate the relative risk (RR) and 95% confidence interval (CI) for the relation between each medication and PD, while accounting for age, sex, race/ethnicity, smoking, and healthcare utilization.

Results:

Beneficiaries taking tacrolimus (RR 0.50, CI 0.40-0.61), everolimus (RR 0.35 CI 0.23-0.53), sirolimus (RR 0.59, CI 0.37-0.95), cyclosporine (RR 0.92, CI 0.74-1.14), mycophenolate (RR 0.77, CI 0.68-0.86), lenalidomide (RR 0.68, CI 0.60-0.78), or ustekinumab (RR 0.82, CI 0.56-1.22) before PD diagnosis or control selection had a lower risk of developing PD when compared to those who did not take these mediations.

Conclusions:

Medications from classes associated with lower risk of PD included corticosteroids, biologics, antimetabolites, and inhibitors of IMDH, JAK, MTOR, dihydrofolate reductase, and calcineurin. The medications within these classes act through mechanisms that target T cells, protein synthesis, the autophagic pathway, and their downstream effects. These medication classes might have potential as disease modifying therapies for PD.