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Original Investigation
August 2018

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

Author Affiliations
  • 1Department of Genetics and Genomic Sciences, ISMMS (Icahn School of Medicine at Mount Sinai), New York, New York
  • 2Division of Gastroenterology, Department of Medicine, ISMMS, New York, New York
  • 3Department of Neurology, ISMMS, New York, New York
  • 4AbbVie Inc, North Chicago, Illinois
JAMA Neurol. 2018;75(8):939-946. doi:10.1001/jamaneurol.2018.0605
Key Points

Question  Among patients with inflammatory bowel disease, what is the incidence of Parkinson disease, and does earlier exposure to anti–tumor necrosis factor therapy mitigate their risk of Parkinson disease?

Findings  In this cohort study analyzing administrative claims from more than 170 million health care–covered lives, patients with inflammatory bowel disease were 28% more likely than matched individuals without inflammatory bowel disease to develop Parkinson disease. Patients with inflammatory bowel disease exposed to antitumor necrosis factor therapy had a 78% reduction in Parkinson disease incidence rates compared with unexposed patients.

Meaning  Reducing systemic inflammation in at-risk individuals may decrease the incidence of Parkinson disease.


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.