Background: Epidemiological studies have suggested a link between rheumatoid arthritis and Parkinson's disease (PD). Disease-modifying anti-rheumatic drugs (DMARDs) might explain this association.
Objective: To evaluate the association between DMARDs and risk of PD in persons with rheumatoid arthritis.
Methods: Nested nationwide case-control study was conducted within the Finnish Parkinson's disease (FINPARK) cohort that includes 22,189 Finnish persons with clinically verified PD diagnosed in 1996-2015. The cases had recorded diagnosis of PD in the Special Reimbursement Register and had no exclusion diagnoses whose symptoms may be confused with PD within two years of PD diagnosis. This study included cases with PD diagnosed during 1999-2015 and rheumatoid arthritis diagnosed >3 years before PD. Rheumatoid arthritis was identified using Finnish Care Register for Health Care and Special Reimbursement Register. Cases were matched with up to seven control persons by age, sex, duration of rheumatoid arthritis and region. DMARDs were categorised into five classes and data on purchased prescriptions was 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. Majority (> 60%) were women and 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 three-year lag period applied between exposure and outcome, except chloroquine/hydroxychloroquine which associated with decreased risk (adjusted odds ratio 0.74; 95% confidence interval 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 as 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 as well as 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).