番茄社区

Corticosteroids and inosine monophosphate dehydrogenase (IMDH) inhibitors may lower the risk of Parkinson disease (PD), a case-control study of Medicare Part D prescription drug data suggests.

Patients using IMDH inhibitors were about one-third less likely to be diagnosed with PD than those taking no immunosuppressant drugs, while patients taking corticosteroids had 20% less risk, reported Brad Racette, MD, of Washington University School of Medicine in St. Louis, and colleagues in .

"This study adds to the existing literature on the role of neuroinflammation in PD," Racette told 番茄社区. "There is considerable evidence that inflammation plays a critical role in PD progression. Our work suggests that it may be possible to modify disease risk by modulating the immune system."

Previous research has suggested that Parkinson's disease and inflammation may be linked; a recent analysis showed that patients with inflammatory bowel disease had an almost 30% higher incidence of PD.

"The role of neuroinflammation in PD is of great interest both from a mechanistic and a drug development perspective," commented Clemens Scherzer, MD, of Harvard Medical School, who was not involved in the study.

"We are really just beginning to understand the intricate interplay between neurons and immune cells in PD," Scherzer told 番茄社区. "It is possible that initial neuronal damage triggers an immune response that then exacerbates the neurodegenerative process. This is an intense area of research."

For this study, the researchers analyzed Medicare Part D prescription drug data of patients ages 60 to 90 in 2009, looking at 48,295 incident PD cases and 52,324 controls. The team identified 26 commonly prescribed immunosuppressant drugs representing seven classes of medications. Excluded were prescriptions written 12 months before PD diagnosis (or by a pre-set cutoff date) to rule out possible prescriptions that might have been linked to early signs of the disease.

Most patients were non-Hispanic white, consistent with the demographic profile of the PD population in the United States. The average age was 78.6 in the case group and 76.4 in controls. The researchers observed a greater risk of PD with increasing age and male sex, and lower risk with tobacco use (all P<0.001).

Two classes of drugs were linked to a lower risk of Parkinson disease: IMDH inhibitors (RR 0.64; 95% CI 0.51–0.79) and corticosteroids (RR 0.80; 95% CI 0.77–0.83). Each IMDH inhibitor drug studied consistently was associated with a lower PD risk, while the corticosteroids with the strongest links were ones used for long-term immunosuppression -- prednisone, dexamethasone, and methylprednisolone.

While IMDH inhibitors appeared more protective, their RRs were imprecise because these medications were used infrequently, the authors wrote. The link with corticosteroids was somewhat weaker, and "we cannot completely rule out the possibility that this inverse association is due to confounding by smoking, since corticosteroids are used frequently for pulmonary symptoms related to smoking."

Corticosteroids have multiple immunosuppressive mechanisms, while IMDH inhibitors likely work primarily on T-cell response to antigens, Racette noted. "We can only speculate about the mechanism of neuroprotection, since that is beyond the scope of this pharmacoepidemiology study.

"We speculate that the potential neuroprotective effects we observed could be due to prevention of the inflammatory response to alpha-synuclein aggregation in the brain by blocking T-cell migration into the central nervous system," he continued. "Alternatively, these medications could somehow block peripheral aggregation or migration of alpha-synuclein into the central nervous system."

Scherzer said that the study adds more granular information about various classes of immunomodulatory drugs, including diverse corticosteroids and other classes of immunosuppressants. But a limitation is the cross-sectional, case-control design: "This is less powerful and more susceptible to confounding than longitudinal studies. It will be important to evaluate this further in multiple, large prospective cohorts."