Elevated Risk of Parkinson Disease Found in Rheumatoid Arthritis


Participants with rheumatoid arthritis had a 1.74-fold higher risk of PD compared with those without, raising importance of an elevated risk.

Jihun Kang, MD, PhD, Department of Family Medicine, Kosin University Gospel Hospital

Jihun Kang, MD, PhD

Findings from a population-based study using the Korean National Health Insurance Service database identified links between rheumatoid arthritis (RA) and increased risk of Parkinson disease (PD). In the analysis, those with seropositive RA (SPRA) has a higher risk of PD than those with seronegative RA (SNRA).

Published in JAMA Neurology, the trial enrolled 54,680 patients with RA and matched them 1:5 with age- and sex-matched controls without RA for a total population of 328,080 individuals. RA was 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.

Led by Jihun Kang, MD, PhD, Department of Family Medicine, Kosin University Gospel Hospital, a total of 1093 patients developed PD—803 in the control group and 290 in the RA group—during the follow-up period of 1,481,363.6 person-years, corresponding to a median of 4.3 years (IQR, 2.6-6.4) and a maximum of 9 years after a 1-year lag. This equated to a 1.74-fold (95% CI, 1.52-1.99) increased risk of PD in participants with RA vs controls.

"Further studies are necessary to determine a mechanistic link between RA and PD. The study findings suggest that physicians who care for patients with RA should be aware of the elevated risk of PD and prompt referral to a neurologist should be considered at onset of early motor symptoms of PD in patients with RA without synovitis."

An increased risk of PD was found in patients with SPRA (adjusted HR, 1.95; 95% CI, 1.68-2.26) but not in patients with SNRA (aHR, 1.20; 95% CI, 0.91-1.57). There was no significant interaction between RA and socioeconomic characteristics, health behavior, and comorbid onditions on the risk of PD. Premenopausal women showed a higher odd of RA-PD (aHR, 4.43; 95% CI, 2.05-9.59) than in postmenopausal women (aHR, 1.75; 95% CI, 1.46-2.10; P = .02). Age at menopause onset or HRT did not have a significant interaction with RA in the development of PD in postmenopausal women.

As for the reasons for discrepancies in PD incidence, investigators noted premenopausal women may not have other risk factors for PD, including age and estrogen deficiency. Therefore, the influence of RA could be more prominent in postmenopausal women.

"With respect to the pathologic explanation of the link be- tween SPRA and PD, impairment in autophagic pathways, which normally remove damaged or abnormally modified proteins, might be a shared pathologic process of the 2 conditions," Kang et al wrote. "The role of autophagy in the generation of citrullinated proteins, which are subsequently processed to SPRA- associated citrullinated antigens and consequently become a target of anti–cyclic citrullinated peptide antibodies, has been reported in previous studies."

In exploratory analysis of DMARDs, findings showed that patients with RA who did not use bDMARDs had a higher risk of PD than the contrl group (aHR, 1.78; 95% CI, 1.54-.204), whereas patients with RA who used bDMARDS did not show a higher risk compared with the control group (aHR, 1.16; 95% CI, 0.65-1.05). Of note, this analysis was relatively small, as only 15 patients with PD used bDMARDS or tsDMARDs.

1. Kang J, Eun Y, Jang W, et al. Rheumatoid arthritis and risk of Parkinson disease in Korea. JAMA Neurol. Published online May 1, 2023. doi:10.1001/jamaneurol.2023.0932
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