Immunosuppressants contribute to a reduced risk of Parkinson’s disease in rheumatoid arthritis

Abstract Background Observational studies have suggested a decreased risk of Parkinson’s disease (PD) in patients with rheumatoid arthritis (RA). However, the results are controversial and the biological mechanism underlying this effect remains largely unknown. Methods The effect sizes of five observational studies were summarized to determine the association between RA and PD. A two-step Mendelian randomization (TSMR) analysis was conducted using genome-wide association studies data sets of RA, PD and prescription of non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (IS) and glucocorticoids (GC). A multivariable MR (MVMR) was also performed to verify the impact of prescription history on PD risk. Results Integrated data from observational studies showed that RA was associated with a decreased risk of PD in the European population (effect size = –0.38, P = 0.004). We found that genetically predicted RA was correlated with a decreased risk of PD [odds ratio (OR) = 0.91, P = 0.007]. In the TSMR, RA patients tended to have an increased prescription of GC (OR = 1.16, P = 2.96e − 07) and IS (OR = 1.77, P = 5.58e − 64), which reduced the risk of PD (GC: OR = 0.86, P = 0.0270; IS: OR = 0.82, P = 0.0277), respectively. Further MVMR analysis demonstrated that only IS was linked to a decreased risk of PD (OR = 0.86, P = 0.004). Conclusion This work clarified that patients with RA had a decreased risk of PD, which was partially attributed to the use of IS in RA patients but not GC or NSAIDs.