Perinatal Factors Increase the Likelihood of Eosinophilic Esophagitis

Gencer Kurt, MD

Investigators have identified numerous perinatal factors believed to increase the like likelihood of developing eosinophilic esophagitis (EoE).

A team, led by Gencer Kurt, Aarhus University, identified several potential factors related to EoE from a nationwide cohort in Denmark, in data presented during the American Academy of Allergy, Asthma & Immunology Annual Meeting (AAAAI) 2022.

Risk Factors

Early life exposures are known risk factors of EoE, potentially through alterations in the colonization of the gut microbiome and subsequent dysregulated immune development.

However, the majority of research has occurred at referral centers using retrospective exposure data, meaning most studies are subject to information bias.

In the study, the investigators used a nationwide, registry-based case-control study of perinatal exposures with data collected prospectively through Danish health and administrative registries.

The investigators examined all EoE cases in Denmark involving individuals born between 1997-2018 and matched each case by sex and age with risk set sampling of controls.

The team also obtained data on pregnancy complications, mode of delivery, gestational age at delivery, birth weight, and neonatal intensive care unit (NICU) admission.

Finally, they estimated the odds of EoE, relative to each perinatal factor, adjusting for possible confounders, using conditional logistic regression models.

Gestational Age

Overall, there were 393 cases included in the study and compared to 3659 control participants after exclusions for missing data (n = 23 cases; n = 501 controls).

The strongest association was between gestational age and EoE peaking at 34 weeks compared to 40 weeks (aOR, 2.5; 95% CI, 1.5-4.0) and NICU admission and EoE peaking at 2-3 weeks NICU stay compared to no admission (aOR, 2.4; 95% CI, 1.1-5.5).

There was also a trend observed toward an association between pregnancy complications and EoE (aOR, 1.4; 95% CI, 1.0-1.8).

There was no evidence observed of an association for weight for gestational age or cesarean delivery

“Perinatal factors, particularly preterm delivery and NICU admission, are associated with the development of EoE,” the authors wrote.

A Treatment on the Horizon

New data from the second phase 3 trial on dupilumab for EoE found that biologic significantly improved signs and symptoms of the disease at 24 weeks compared to placebo in patients 12 years and older.

In the recent phase 3 trial, which featured an independent cohort and was twice the size of the previous phase 3 trial, patients on dupilumab saw a 64% reduction in disease symptoms from baseline compared to 41% for placebo (P = 0.0008) and experienced a 23.78 point improvement on the patient-reported Dysphagia Symptom Questionnaire compared to a 13.86 point improvement for placebo (P <0.0001).

To date, dupilumab is the only biologic medicine to show positive, clinically meaningful phase 3 results in adults and adolescents with EoE. Currently, there are no approved treatments for the underlying drivers of the disease.

Over the past 2 decades, estimates have shown an increasing prevalence of EoE. Of the roughly 160,000 patients in the US who are currently being treated, however, approximately 48,000 have failed multiple treatments.

Typical treatments include proton pump inhibitors, topical steroids, and diet elimination, many of which are not sufficient for up to 30-40% of EoE patients.

The study, “Perinatal Factors Increase Risk of Eosinophilic Esophagitis – A Nationwide Case-Control Study,” was published online in the Journal of Allergy and Clinical Immunology.