Anti–Tumor Necrosis Factor Therapy and Incidence of Parkinson Disease Among Patients With Inflammatory Bowel Disease

This is a really interesting study. It looks at the relationship between inflammatory bowel disease and Parkinson's disease, which is something I have been wanting to do for sometime. There is lots of seemingly circumstantial evidence linking IBD and PD, including gastrointestinal inflammation, unusual relationships with smoking (for ulcerative colitis) and an association with the LRRK2 gene (for Crohn's disease). Here the authors show an association between PD and all IBD, and between PD and Crohn's disease and ulcerative colitis separately. People with IBD appeared to be at increased risk of PD during follow-up...

Perhaps more intriguing is that fact that they show a reduction in that increased risk if people were treated with drugs targeted against the mechanisms of IBD. Whether this represents a reduction in risk because the IBD is better treated or because the same drugs target a pathway that is important to PD remains to be seen....

Inga Peter, PhD; Marla Dubinsky, MD; Susan Bressman, MD; Andrew Park, PhD, MPH; Changyue Lu, MS; Naijun Chen, MS; Anthony Wang, PhD, MPH

JAMA Neurology 23rd April 2018

https://jamanetwork.com/journals/jamaneurology/fullarticle/2679038

Importance
Despite established genetic and pathophysiologic links between inflammatory bowel disease (IBD) and Parkinson disease (PD), clinical data supporting this association remain scarce. Although systemic inflammation is considered a potential biological mechanism shared between the 2 diseases, the role of reduced systemic inflammation through IBD-directed anti–tumor necrosis factor (anti-TNF) therapy in PD risk is largely unknown.

Objective
To compare the incidence of PD among individuals with or without IBD and to assess whether PD risk among patients with IBD is altered by anti-TNF therapy.

Design, Setting, and Participants 
This is a retrospective cohort study analyzing information in the Truven Health MarketScan administrative claims database and the Medicare Supplemental Database between January 1, 2000, and March 31, 2016. Individuals were selected who had at least 2 claims for IBD diagnoses, at least 6 months of follow-up, and no prior diagnosis of PD on or before the IBD index date. Exposure to Anti-TNF therapy was measured from the anti-TNF index date to the last date of anti-TNF coverage or the end of enrollment or PD index date, whichever was earliest. Incidence rates per 1000 person-years were calculated, and crude and adjusted incidence rate ratios were estimated by Poisson regression models and presented with 95% CIs.

Main Outcomes and Measures 
Incidence of PD among patients with IBD with or without exposure to anti-TNF therapy.

Results
In total, 144 018 individuals with IBD were matched on age, sex, and year of index date with 720 090 unaffected controls. Of them, 1796 individuals had at least 2 PD diagnoses and at least 1 filled PD-related prescription. The mean (SD) age of individuals with IBD was 51 (17) years, and 44% were men. The incidence of PD among patients with IBD was 28% higher than that among unaffected matched controls (adjusted incidence rate ratio, 1.28; 95% CI, 1.14-1.44; P < .001). A 78% reduction in the incidence rate of PD was detected among patients with IBD who were exposed to anti-TNF therapy compared with those who were not exposed (adjusted incidence rate ratio, 0.22; 95% CI, 0.05-0.88; P = .03).

Conclusions and Relevance 
A higher incidence of PD was observed among patients with IBD than among individuals without IBD. Early exposure to antiinflammatory anti-TNF therapy was associated with substantially reduced PD incidence. These findings support a role of systemic inflammation in the pathogenesis of both diseases. Further studies are required to determine whether anti-TNF treatment administered to high-risk individuals may mitigate PD risk.