medwireNews: Overall use of DMARDs or corticosteroids is not associated with a reduced risk for Parkinson’s disease (PD) in people with rheumatoid arthritis (RA), but chloroquine or hydroxychloroquine use may be, show results of a nationwide case-control study.
Anne Paakinaho (University of Eastern Finland, Kuopio) and co-investigators say their “results suggest that the lower risk of PD in people with rheumatoid arthritis is not explained by DMARD use.”
The study included data for 315 individuals with clinically verified PD diagnosed at least 3 years after RA and 1571 controls with RA but no Parkinson’s disease, matched for age, sex, RA duration, and region.
Prior to the 3-year lag period preceding PD diagnosis, the most commonly used DMARDs in both cases and controls were sulfasalazine (51.1 and 50.5%, respectively), methotrexate (51.8 and 47.8%), and chloroquine or hydroxychloroquine (37.5 and 44.8%).
Gold preparations were used by approximately one quarter of cases and controls during this period and immunosuppressants were used by 15–17%. In addition, approximately two-thirds of cases and controls used corticosteroids.
As reported in Neurology, there was no significant association between the use of sulfasalazine, methotrexate, gold preparations, immunosuppressants, or corticosteroids before the 3-year lag period and the risk for PD. There were also no significant associations when DMARD use was assessed only in the 3-year lag period, or at any time before PD diagnosis.
There was, however, a link between chloroquine or hydroxychloroquine use and PD risk. Specifically, chloroquine or hydroxychloroquine use was significantly less common in the PD cases versus controls, and after adjustment for potentially confounding comorbidities, the risk for PD was a significant 26% lower for people who used these agents before the 3-year lag period relative to those who did not. In addition, the PD risk was a significant 31% lower with chloroquine or hydroxychloroquine use at any time relative to no use.
Paakinaho and team explain that both chloroquine and hydroxychloroquine “interfere with lysosomal activity and autophagy, can inhibit both innate and adaptive immune processes and reduce production of inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF).”
They suggest that these mechanisms could modulate inflammatory processes in PD but note that methotrexate is a “more powerful immunosuppressant than hydroxychloroquine [and] was not associated with risk of PD in our study.”
Therefore, “[t]he potential ability of chloroquine/hydroxychloroquine to modify the PD disease process should be studied further,” the authors remark.
They also suggest: “Further studies on newer DMARDs, especially on [biologic] DMARDs such as TNF-α inhibitors and target specific DMARDs (JAK inhibitors), and assessment of dose-response relations between DMARDs and risk of PD are needed.”
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