To evaluate the association between Parkinson’s disease (PD) and rheumatoid arthritis (RA) using a systematic meta-analysis of observational studies.

PD and RA are chronic disorders with distinct clinical phenotypes but overlapping immunological and inflammatory pathways. Epidemiologic studies have reported conflicting associations, with some suggesting increased PD risk in RA due to systemic inflammation, while others indicate a protective effect possibly related to immune modulation or anti-inflammatory therapy. Clarifying this relationship is critical for understanding shared pathophysiology and identifying potential therapeutic targets.

We systematically searched PubMed and Embase for observational studies reporting RA incidence in PD patients (PD→RA) or PD incidence in RA patients (RA→PD). Twelve studies met inclusion criteria (4 PD→RA; 8 RA→PD). Data were pooled using a binary outcome meta-analysis with the Mantel-Haenszel method under a random-effects model (DerSimonian-Laird estimator). Risk ratios (RR) with 95% confidence intervals (CI) were calculated. Between-study heterogeneity was assessed using τ², I², and Cochran’s Q test. Publication bias was evaluated using Egger’s regression, Begg’s rank correlation, and trim-and-fill analysis.

The overall random-effects model showed no significant association (effect size = −0.007; 95% CI: −0.25 to 0.24; p = 0.95), with low heterogeneity (τ² = 0.15; I² = 1%). Subgroup analysis revealed that PD was associated with a reduced risk of RA (RR = 0.69; 95% CI: 0.53–0.89), whereas RA was associated with a modestly increased risk of PD (RR = 1.23; 95% CI: 1.04–1.45). Publication bias tests were non-significant (Egger’s p = 0.68; Begg’s p = 0.58), although trim-and-fill suggested one potentially missing study.

PD appears inversely associated with RA risk, while RA is linked to a slight increase in PD risk. These findings underscore complex immune-neurodegenerative interactions and warrant mechanistic studies to clarify shared pathways and therapeutic implications.