Two recent studies found a link between inflammatory bowel disease (IBD) and Parkinson's disease, one suggesting that anti-tumor necrosis factor (TNF) therapy may lower risk of developing the neurodegenerative disorder.
In the first study, researchers compared all patients diagnosed with IBD in Denmark between 1977 and 2014 (n=76,477) to about 7.5 million non-IBD controls who were similar in gender, age, and vital status to see if IBD was associated with risk of Parkinson's disease and multiple system atrophy. Results were published online on May 21 by Gut.
After adjustment for comorbidity index, patients with IBD had a 22% increased risk of Parkinson's disease compared to individuals without IBD (hazard ratio, 1.22; 95% CI, 1.09 to 1.35) over more than 8 million person-years of follow-up. The greater risk was independent of age at IBD diagnosis, gender, or length of follow-up. Researchers also found a higher risk of developing multiple system atrophy in the IBD cohort compared to the non-IBD individuals (hazard ratio, 1.41; 95% CI, 0.82 to 2.44), although overall incidence was low.
The increased risk of both disorders was slightly higher in patients with ulcerative colitis (hazard ratio, 1.35; 95% CI, 1.20 to 1.52) than in those with Crohn's disease (hazard ratio, 1.12; 95% CI, 0.89 to 1.40). Therefore, patients with ulcerative colitis had a 3% higher risk of Parkinson's disease and multiple system atrophy than patients with Crohn's disease (hazard ratio, 1.035; 95% CI, 1.03 to 1.04; P<0.001).
Limitations of the study include its registry-based nature, the researchers' inability to access medication data, and unmeasured confounders such as smoking, the study authors noted. “Although the absolute risk of [Parkinson's disease] remains low, our study points to overlapping pathogenic mechanisms, which merit further investigation, as they may represent targets for future therapeutic interventions,” they wrote.
Such therapeutic interventions may already exist, the second study suggested. Using data from two U.S. claims databases between Jan. 1, 2000, and March 31, 2016, researchers assessed the incidence of Parkinson's disease among patients with IBD with or without exposure to anti-TNF therapy. Patients had at least two claims for IBD diagnoses, at least six months of follow-up, and no prior diagnosis of Parkinson's disease.
Results of the industry-supported study were published online on April 23 by JAMA Neurology.
Researchers matched 144,018 individuals with IBD with 720,090 unaffected controls and found that patients with IBD had a 28% higher incidence of Parkinson's disease than controls (adjusted incidence rate ratio, 1.28; 95% CI, 1.14 to 1.44; P<0.001). Among patients with IBD who were exposed to anti-TNF therapy, there was a 78% reduction in the incidence rate of Parkinson's disease compared to those who were not exposed (adjusted incidence rate ratio, 0.22; 95% CI, 0.05 to 0.88; P=0.03).
“Although our study design does not allow for inferring causality, we hypothesize that a reduction of systemic inflammation contributed to the observed association,” the study authors wrote. They noted limitations of the study, such as a lack of diagnostic clinical criteria to identify cases and the small number of events in the anti-TNF-exposed cohort.
The study “provides exciting evidence in support of the concept of virtual repurposing of old drugs for new benefits. It turns pre-existing TNF inhibitor pipelines for treatment of IBD into potential research and development goldmines for treatment of [Parkinson's disease],” according to an accompanying editorial.