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

摘要

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.