Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease: Nested Case-Control Study of People With Rheumatoid Arthritis

Background And Objectives: Epidemiologic studies have suggested a link between rheumatoid arthritis and Parkinson disease (PD). Disease-modifying antirheumatic drugs (DMARDs) might explain this association. The aim of this work was to evaluate the association between DMARDs and risk of PD in persons with rheumatoid arthritis.

Methods: This nested nationwide case-control study was conducted within the Finnish Parkinson's Disease (FINPARK) cohort, which includes 22,189 Finnish persons with clinically verified PD diagnosed in 1996 to 2015. The cases had recorded diagnosis of PD in the Special Reimbursement Register and had no exclusion diagnoses with symptoms that may be confused with PD within 2 years of PD diagnosis. This study included cases with PD diagnosed during 1999 to 2015 and rheumatoid arthritis diagnosed >3 years before PD. Rheumatoid arthritis was identified from the Finnish Care Register for Health Care and Special Reimbursement Register. Cases were matched with up to 7 controls by age, sex, duration of rheumatoid arthritis, and region. DMARDs were categorized into 5 classes, and data on purchased prescriptions were identified from the Prescription Register since 1995. Associations were studied with conditional logistic regression adjusted for confounders.

Results: Altogether, 315 cases with PD and 1,571 matched controls were included. The majority (>60%) were women, and the median duration of rheumatoid arthritis on matching date was 11.6 years for controls and 12.6 years for cases. Use of DMARDs was not associated with risk of PD with a 3-year lag period applied between exposure and outcome except chloroquine/hydroxychloroquine, which associated with decreased risk (adjusted odds ratio [OR] 0.74, 95% confidence interval [CI] 0.56-0.97). Other DMARDs, including sulfasalazine, methotrexate, gold preparations, and immunosuppressants, were not associated with PD.

Discussion: Our results suggest that the lower risk of PD in people with rheumatoid arthritis is not explained by DMARD use because these drugs in general did not modify the risk of PD among persons with rheumatoid arthritis. Association between chloroquine/hydroxychloroquine and lower risk of PD and the possible underlying mechanisms should be further investigated.

Classification Of Evidence: This study provides Class II evidence that in individuals with rheumatoid arthritis using DMARDs, only chloroquine/hydroxychloroquine was associated with a potentially decreased risk of developing PD (adjusted OR 0.74, 95% CI 0.56-0.97).