Early Mebendazole Exposure May Increase Adult-Onset UC Risk

Mebendazole exposure to treat helminth infestations prior to age 5 increases the risk for adult-onset, but not pediatric-onset, ulcerative colitis (UC), according to study findings published in the American Journal of Gastroenterology.

Researchers conducted a population-based cohort study to determine whether early exposure to mebendazole therapy increased future risk of developing inflammatory bowel disease (IBD).

Researchers used the Danish Civil Registration System (CRS) to prospectively collect data on 1,520,290 individuals born in Denmark between January 1, 1995 and December 31, 2018.

CRS identification numbers were cross-linked to corresponding numbers in the Danish National Prescription Register to identify 615,794 patients exposed to mebendazole before 18 years of age for the treatment of helminth parasitic infestations. Of these patients, 348,934 received mebendazole treatment prior to age 5.

Mebendazole exposure prior to age 18 did not increase risk of developing either pediatric- or adult-onset IBD (hazard ratio [HR], 0.98; 95% CI, 0.88-1.09 and HR, 1.09; 95% CI, 0.99-1.21, respectively).

Similarly, mebendazole exposure prior to age 5 also did not increase risk of developing pediatric-onset IBD (HR, 0.98; 95% CI, 0.87-1.11); however, it was associated with adult-onset IBD (HR, 1.18; 95% CI, 1.05-1.32).

When analyzing IBDs by subgroup, the researchers found that early mebendazole exposure prior to age 5 increased the likelihood of developing adult-onset UC (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.12-1.56), but not Crohn disease (CD) [aHR, 1.04; 95% CI, 0.88-1.23].

Per IBD subgroup analysis, mebendazole exposure prior to age 5 did not increase risk of developing either CD (aHR, 0.96; 95% CI, 0.81-1.13) or UC (aHR, 1.02; 95% CI, 0.85-1.22).

Study limitations include possible misclassification of exposure, misclassification of outcomes, and the risk for unmeasured and residual confounding due to the observational and historical nature of the study’s design.

 “Our finding that mebendazole exposure increases UC risk only when it occurs at < 5 years of age is novel and further underscores the relevance of the early life period towards immune modulation and risk of future IBD,” the study authors noted. “The Developmental Origins of Health and Disease hypothesis suggests that the early life period is a critical window of susceptibility, and upon exposure to various environmental agents, the developing fetus and young child develop adaptive immune responses, which carry long term health consequences.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.