Rheumatoid Arthritis and Risk of Parkinson Disease in Korea

Abstract

Importance: Although it has been postulated that chronic inflammation caused by rheumatoid arthritis (RA) contributes to the development of Parkinson disease (PD), the association between these 2 conditions has yet to be determined.

Objective: To evaluate the association between RA and subsequent PD risk.

Design, setting, and participants: This retrospective cohort study used the Korean National Health Insurance Service database to collect population-based, nationally representative data on patients with RA enrolled from 2010 to 2017 and followed up until 2019 (median follow-up, 4.3 [IQR, 2.6-6.4] years after a 1-year lag). A total of 119 788 patients who were first diagnosed with RA (83 064 with seropositive RA [SPRA], 36 724 with seronegative RA [SNRA]) were identified during the study period and included those who underwent a national health checkup within 2 years before the RA diagnosis date (64 457 patients). After applying exclusion criteria (eg, age <40 years, other rheumatic diseases, previous PD), 54 680 patients (39 010 with SPRA, 15 670 with SNRA) were included. A 1:5 age- and sex-matched control group of patients without RA was also included for a total control population of 273 400.

Exposures: Rheumatoid arthritis as defined using International Classification of Diseases, Tenth Revision codes M05 for SPRA and M06 (except M06.1 and M06.4) for SNRA; prescription of any disease-modifying antirheumatic drug; and enrollment in the Korean Rare and Intractable Diseases program.

Main outcomes and measures: The main outcome was newly diagnosed PD. Data were analyzed from May 10 through August 1, 2022, using Cox proportional hazards regression analyses.

Results: From the 328 080 individuals analyzed (mean [SD] age, 58.6 [10.1] years; 74.9% female and 25.1% male), 1093 developed PD (803 controls and 290 with RA). Participants with RA had a 1.74-fold higher risk of PD vs controls (95% CI, 1.52-1.99). An increased risk of PD was found in patients with SPRA (adjusted hazard ratio [aHR], 1.95; 95% CI, 1.68-2.26) but not in patients with SNRA (aHR, 1.20; 95% CI, 0.91-1.57). Compared with the SNRA group, those with SPRA had a higher risk of PD (aHR, 1.61; 95% CI, 1.20-2.16). There was no significant interaction between covariates on risk of PD.

Conclusions and relevance: In this study, RA was associated with an increased risk of PD, and seropositivity of RA conferred an augmented risk of PD. The findings suggest that physicians should be aware of the elevated risk of PD in patients with RA and promptly refer patients to a neurologist at onset of early motor symptoms of PD without synovitis.

Figure 1.. Flow Diagram of Study Participants

PD indicates Parkinson disease; RA, rheumatoid arthritis; SNRA, seronegative rheumatoid arthritis; SPRA, seropositive rheumatoid arthritis.

Figure 2.. Cumulative Incidence of Parkinson Disease (PD) According to Rheumatoid Arthritis (RA) Status and Serologic Status of RA

SNRA indicates seronegative rheumatoid arthritis; SPRA, seropositive rheumatoid arthritis.