Patients With EoE Lack Effective, Targeted Therapies for Long-term Disease Control, Review Finds

There is a growing understanding of the underlying type 2 inflammation that contributes to eosinophilic esophagitis (EoE). Although current treatments can be effective, there remains a need for targeted systemic therapies, according to a review of the disease and unmet treatment needs published in The American Journal of Gastroenterology.

In addition to impaired quality of life (QOL) due to symptoms, patients with EoE suffer from social and psychological implications of food-related illness and the costs of treatment. Current treatments may not provide long-term disease control.

“Targeted therapies are needed to restore the esophageal barrier, normalize the immune response to triggers, reduce chronic inflammation, and limit or prevent progression of remodeling and fibrosis to restore esophageal function and reduce patient burden,” the authors explained. “Additionally, there is an unmet need for earlier diagnosis, defined treatment outcomes, and a greater understanding of patient perspectives on treatment.”

During their review of the progression and pathophysiology of EoE over the course of a patient’s life, the researchers held 2 advisory board meetings and discussions with key opinion leaders. They also conducted a literature search for previous studies and reviews assessing EoE disease burden and unmet need.

The authors found the increasing prevalence and incidence of EoE is only partly explained by improved diagnostics and disease recognition and that the increase in cases has outpaced increases in biopsy and detection. The fact that patients with EoE are predominantly White males and there is an increased relative risk within families “suggests genetic risk,” they noted.

The studies they evaluated found younger patients with comorbid atopic conditions and food allergies tended to have the inflammatory phenotype compared with older patients who have more fibrostenotic complications. The studies also found delays in diagnosis and lapses in follow-up contribute to an increased likelihood of fibrostenotic complications.

“For every 10-year increase in age, the odds of having a fibrostenotic phenotype more than doubles, suggesting a natural history of disease progressing from a largely inflammatory to a more fibrostenotic phenotype over time,” the authors wrote. “However, there is significant diversity in the pattern and rate of disease progression, and fibrostenosis has been observed in children.”

In adults and children 10 years or older, dysphagia and food impaction are the primary clinical manifestations, and they substantially impair QOL.

First-line therapies for EoE include dietary restrictions or elimination diets, swallowed topical corticosteroids (STCs), proton pump inhibitors (PPIs), and dilation of the esophagus. Approximately two-thirds of patients on PPIs and one-third of patients on STCs fail to achieve histologic remission, and there are no good predictors of therapeutic response at this time, the authors explained. While STCs are more effective at inducing histologic response than PPIs and are generally well tolerated in the short and long term, there are cumulative adverse effects that can be concerning.

“Additional research is needed to understand which therapy is best as initial treatment for patients of different phenotypes and prospective trials designed to evaluate combination therapy are needed,” they wrote. “Regardless of first-line therapy choice, shared decision-making with patients is key to securing adherence and optimal outcomes.”

Finally, elimination diets are not only difficult to maintain in the long term but can also be expensive.

There are novel emerging therapies:

• Both mepolizumab and reslizumab target interleukin (IL)-5 and are currently prescribed for severe eosinophilic asthma; however, despite showing histologic improvements in EoE, they failed to induce symptomatic improvement
• Omalizumab is a humanized mouse anti–immunoglobulin E antibody currently used for severe allergic asthma, but it showed no improvement in EoE symptoms and no reduction in eosinophils
• Cendakimab targets IL-13 and reduced eosinophil counts and improved histologic and endoscopic outcomes, but was unable to significantly improve dysphagia symptoms in a phase 2 trial; there is a phase 3 trial in progress
• Lirentelimab is a monoclonal antibody (mAb) that was associated with dysphagia improvement in a subset of patients in a phase 2 trial, but in a phase 2/3 trial, symptom improvement was not achieved
• Dupilumab, a fully human mAb, inhibits IL-4 and IL-13 and improved peak esophageal intraepithelial eosinophil count, dysphagia, and disease-specific health-related QOL in addition to reducing symptom burden over 52 weeks of treatment in adults; the therapy was also well tolerated and there is an ongoing phase 3 trial in children
• Benralizumab, another IL-5 inhibitor, has an ongoing study in EoE

The authors noted that many patients with EoE switch therapies, highlighting the need for more optimal long-term management. However, tailoring treatment requires a better understanding of patient subgroups who are likely to respond to specific therapies.

“EoE is a complex, heterogenous disease, with increasing prevalence worldwide. There is an emerging understanding of the underlying type 2 inflammation contributing to disease features and progression,” the authors concluded. “Given the discordance between symptoms, histology, and endoscopic features, there is a need for comprehensive treat-to-target goals, individualized therapy, and continuous monitoring of treatment response.”

Reference

Bredenoord AJ, Patel K, Schoepfer AM, et al. Disease burden and unmet need in eosinophilic esophagitis. Am J Gastroenterol. Published online April 13, 2022. doi:10.14309/ajg.0000000000001777