April 25, 2018
By Will Boggs MD
NEW YORK (Reuters Health) - Patients with inflammatory bowel disease (IBD) who receive anti-tumor necrosis factor (TNF) therapy have a reduced incidence of Parkinson’s disease (PD), compared with nonusers, according to a retrospective study.
"Anti-TNFalpha therapy has been contemplated for neurodegenerative diseases (though not Parkinson’s) without much success, mostly attributable to it not crossing the blood-brain barrier (BBB)," said Dr. Inga Peter from Icahn School of Medicine at Mount Sinai, in New York City.
"Our results suggest that the timing could be critical. If exposed earlier in life, it could be protective, as opposed to a means to treat the disease," she told Reuters Health by email.
PD and IBD share a number of genetic and functional features, but there are limited data on comorbid PD and IBD.
Dr. Peter's team used data from the Truven Health MarketScan Commercial Database and the Medicare Supplemental Database to assess the incidence of PD among patients with IBD and to identify whether IBD treatment with anti-TNF is linked to the risk of PD.
The incidence of PD was 28% higher among patients with IBD (0.73%) than among matched controls without IBD (0.57%), with similarly increased rates among patients with Crohn's disease and among those with ulcerative colitis.
The difference in PD incidence was apparent only among men with IBD (0.34% vs. 0.25% among men without IBD), and not among women (0.19% vs. 0.16%, respectively), the researchers report in JAMA Neurology, online April 23.
Among patients with IBD, the incidence of PD was significantly lower in those exposed to anti-TNF therapy (0.08 per 1,000 patient-years) than in those not exposed to anti-TNF therapy (0.76 per 1,000 patient-years).
Exposure to anti-TNF therapy was associated with a 78% reduction in the incidence of PD after adjustment for age group and sex (P=0.03).
"Systemic inflammation could play a more significant role in the development of Parkinson’s disease (not just local inflammation in the brain), and targeting systemic inflammation earlier in life could reduce the risk of Parkinson’s," Dr. Peter speculated. "The drugs may not necessarily have to cross the BBB, unless the BBB is leaky in patients with IBD, and then it would only help prevent Parkinson’s disease in IBD patients."
"We need to better understand who among patients with IBD is at risk of Parkinson’s disease (particular mutation carriers?) and test whether our findings hold up in patients with other immune-mediated diseases who are treated with anti-TNFalpha therapy," she said.
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Dr. Clemens R. Scherzer from Brigham and Women's Hospital and Harvard Medical School in Boston, who co-authored a linked editorial, told Reuters Health by email, "Turning big health data into 'virtual drug trials' is an innovative approach for drug discovery. This suggested anti-TNF drugs as candidate drugs for PD based on the analysis of large U.S. claims databases in the study by Peter (et al). Previously, in our own work, we used a similar 'virtual drug trial' to discover a link between an asthma drug (the beta2-agonist salbutamol) and reduced risk of PD based on health data for the entire population of Norway."
"TNF is a potential therapeutic target for PD, but we need mechanistic and clinical studies before it is ready for prime time in PD," he said.
Dr. Marcus M. Unger from Universitaetsklinikum des Saarlandes, in Homburg/Saar, Germany, recently reported elevated fecal markers of intestinal inflammation in PD. He told Reuters Health by email, "This study endorses hypotheses suggesting that intestinal inflammation contributes to the development of PD."
"In the long run, anti-inflammatory therapeutic approaches might become relevant for early (pre-motor) PD," said Dr. Unger, who was not involved in the new work. "The big question will be whether it is already too late for such an intervention when the patient is symptomatic."
Dr. Brad A. Racette from Washington University School of Medicine, St. Louis, Missouri, told Reuters Health by email, "In our recent study of PD and IBD, we found similar results when looking at the overall IBD-PD association, i.e., a positive association, until we adjusted for health care utilization. With adjustment we instead observed an inverse association, which is more consistent with the current paper’s findings that IBD treatments possibly might reduce PD risk."
"This adjustment is important because people who access the healthcare system more frequently have more opportunities to be diagnosed with PD," he explained. "The authors appropriately acknowledge that they could not adjust for access to medical care, nor for race and smoking, both of which also are strongly associated with PD and can confound the relationship between PD and other diseases."
"The number of anti-TNF treated patients who developed PD is very small (only two), so these results must be viewed with some caution," Dr. Racette said. "Also, it is unknown the extent to which anti-TNF agents caused this reduction in PD risk, as opposed to simply serving as a marker of more severe IBD requiring a variety of anti-inflammatory treatments."
AbbVie employed three of the authors and had various relationships with two others, but otherwise had no role in the design or conduct of the study.
SOURCE: https://bit.ly/2HuYhgC and https://bit.ly/2qZIDTH
JAMA Neurol 2018.
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