Anti-TNF Therapy Reduces Parkinson Incidence in Patients with IBD

Inga Peter, MD, from the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai

Inga Peter, MD

The reduction of systemic inflammation in those at-risk for Parkinson disease may decrease the incidence of the condition, according to the findings of a cohort study.¹

Led by Inga Peter, MD, from the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, in New York, the group of researchers sought out to compare the incidence of Parkinson among individuals with or without inflammatory bowel disease (IBD)—as there are established links between the two—and to see if anti-tumor necrosis factor (anti-TNF) therapy could alter the risk of Parkinson in those with IBD.

The retrospective cohort study revealed that those exposed to anti-TNF therapy had an incidence rate of Parkinson that was 78% lower than those who were not exposed (adjusted incidence ratio, 0.22; 95% CI, 0.05 to 0.88; P = .03).

“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-TNF] therapy in PD risk is largely unknown,” Peter and colleagues noted.

Peter and colleagues analyzed data from the Medicare Supplemental Database between January 1, 2000, and March 31, 2016, to identify 144,018 individuals with IBD and 720,090 controls. In total, 1796 had ≥2 diagnoses of Parkinson and ≥1 filled prescription related to it. The incidence of Parkinson was 28% higher in the group with IBD compared to the controls (adjusted incidence rate ratio, 1.28; 95% CI, 1.14 to 1.44; P <.001).

In total, 13,089 patients with IBD were exposed to anti-TNF therapy on or after the IBD index date, with the overall observed incidence rate of Parkinson being markedly lower with those exposed. The group exposed to anti-TNF therapy had an incidence rate of 0.08 per 1000 patient-years compared to 0.76 per 1000 patient-years among patients who were not exposed to the therapy.

In an accompanying editorial, Abby L. Olsen, MD, PhD; Trond Riise, PhD; and Clemens R. Scherzer, MD, noted that “[conducting] a prevention trial for PD from scratch would be incredibly difficult and expensive. It has never been done, although several prevention trials are on the way for Alzheimer disease,” so in place of undertaking a monumental effort such as that, “Peter and colleagues nimbly queried existing longitudinal data of more than 170 million people in claims databases. They assessed whether administration of anti—tumor necrosis factor (anti-TNF), an effective therapy for IBD, would modify the risk of PD. Excitingly, their data suggested that it just might.”²

Systemic inflammation, which Peter and colleagues noted as a major factor of IBD, is additionally believed to be a contributor to neuronal inflammation and dopaminergic neuron loss seen in Parkinson, through the permeation and buildup of immune cells from the periphery. “Intraperitoneal injection of bacterial lipopolysaccharide—shown to produce a systemic immune response in mice and to increase intestinal permeability, an important pathogenic factor of IBD&mdash;has also resulted in microglial activation and dopaminergic neuron loss,” they wrote. Due to lipopolysaccharide’s inability to enter the brain, an increase in systemic cytokine production as a response to dispensed lipopolysaccharide is, according to the authors, a likely contributor to neuroinflammation, through the transportation of TNF and interleukin 1 across the blood-brain barrier.

“Early exposure to [anti-inflammatory] 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 [Parkinson] risk,” Peter and colleagues concluded.

REFERENCES

1. Peter I, Dubinsky M, Bressman S, et al. Anti—Tumor Necrosis Factor Therapy and Incidence of Parkinson Disease Among Patients With Inflammatory Bowel Disease. JAMA Neurol. 2018;75(8):939—946. doi: 10.1001/jamaneurol.2018.0605.

2. Olsen AL, Riise T, Scherzer CR. Discovering New Benefits From Old Drugs With Big Data—Promise for Parkinson Disease. JAMA Neurol. 2018;75(8):917—920. doi: 10.1001/jamaneurol.2018.0345.