(26) Identification of Drugs Associated with Lower Risk of Parkinson's Disease Using Systematic Screening Approach in a Nationwide Nested Case-Control Study

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1071

Presenting Author(s)

Anna-Maija Tolppanen
– professor, Kuopio, Pohjois-Savo, Finland

Co-Author(s)

Marjaana Koponen
– School of Pharmacy, University of Eastern Finland, Kuopio, Finland, Finland
Anne Paakinaho
– University of Eastern Finland, Kuopio, Pohjois-Savo, Finland
Julian Lin
– School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland, Finland
Sirpa Hartikainen
– Professor, School of Pharmacy, University of Eastern Finland, Kuopio, Finland, Kuopio, Pohjois-Savo, Finland

Background: Drugs for other indications may be repurposable as disease-modifying drugs for Parkinson’s disease (PD). Systematic hypothesis-free approach can enable identification of candidates.

Objectives: To identify drugs associated with lower risk of PD by systematic investigation of drugs used in a nationwide nested case-control study of people with clinically verified PD diagnosis.

Methods: The Finnish Parkinson’s disease study (FINPARK) was randomly split to screening (10183 cases and 67849 controls) and replication (10184 cases and 67754 controls) samples, including cases diagnosed in 1998-2015. Exposure on individual-drug as well as group- and subgroup level (3- and 4-character level of Anatomic-Therapeutic Chemical Classification system) was assessed from the Prescription register since 1995. Univariable associations of exposures that had occurred at least three years before the index date (PD diagnosis date of the referent case) were assessed in the screening sample with conditional logistic regression with significance level P=0.1 as threshold. Exposure prior to index date was considered in sensitivity analyses. In confounder-adjusted replication analyses different exposure periods were used.

Results: The results reflect the known risk factors (e.g., smoking and cancer) and the implied role of immune system in PD pathogenesis as well as spurious associations. Two groups (antipsoriatics and antigout preparations) and 4 subgroups (cicatrizants, antipsoriatics for topical use, antigout preparations and mydriatics and cycloplegics) met the screening threshold. The group-level associations were mainly driven by associations of individual drugs. Seven other drugs (for example methotrexate, drugs for chronic obstructive pulmonary disease, COPD) associated with lower risk. In sensitivity analyses, group-level association was observed with antineoplastic drugs, driven by methotrexate. In addition, 3 diabetes drugs and 5 COPD drugs met the screening threshold. Antigout preparations and antipsoriatics were the only exposure whose association was confirmed in replication. Associations of COPD drugs, methotrexate and diabetes drugs were evaluated in indication-restricted designs.

Conclusions: Although the systematic screening is easy to implement, our findings demonstrate the importance of controlling for confounding by indication which is more difficult to apply to systematic screening.