The recent publication of guidelines by the Joint Task Force for the American Academy of Allergy Asthma Immunology and American College of Allergy Asthma Immunology, and the American Gastroenterology Association has provided valuable insights into the management of Eosinophilic Oesophagitis (EoE).

With the regulatory approval of dupilumab as the first medication for EoE, this expert opinion document aims to provide clinicians with a framework for incorporating dupilumab into the treatment strategy for patients with EoE.

Introduction

In 2020, the Joint Task Force for the American Academy of Allergy Asthma Immunology and American College of Allergy Asthma Immunology and the American Gastroenterology Association (JTF-AGA) published guidelines for EoE management. These guidelines serve as a valuable resource for clinicians.

Since their publication, significant advancements have been made, including the approval of dupilumab by the FDA (USA) and EMA (EU). In the USA Dupilumab is the first medication specifically indicated for EoE treatment. This clinical guidance aims to help healthcare professionals integrate dupilumab into their management approach where available for patients with EoE, thereby enhancing treatment strategies and improving outcomes.

Background

Eosinophilic oesophagitis (EoE) is a globally encountered non-immunoglobulin E (IgE)-mediated allergen-driven disease. Its early cases were reported in the late 1970s and early 1980s, with the first cohorts identified in the 1990s. EoE has a male predominance and an estimated prevalence of approximately 1 in 2000. Diagnosis is based on clinical symptoms of oesophageal dysfunction and the presence of more than 15 eosinophils per high power field (hpf) isolated to the oesophagus.

Treatment approaches include dietary therapy, proton pump inhibitors (PPIs), swallowed topical corticosteroids (TCS), and, rarely, oral glucocorticosteroids. The American Gastroenterological Association and the Joint Task Force on Allergy-Immunology Practice Parameters have provided guidelines for these therapies.

The 2020 Guideline: A Comprehensive Overview of Eosinophilic Esophagitis Management

The 2020 guidelines, based on a systematic review, meta-analysis, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) evidence rating, offer valuable insights into treating this complex condition.

Dietary options such as elemental diet, empirical elimination, and allergy test-based diet are conditionally recommended over no treatment, with evidence suggesting improved histologic response. However, it is essential to consider the potential impact on quality of life and dietary adherence when implementing dietary management.

Medical therapies, including the off-label use of PPI and TCS, have also demonstrated improved histologic response in EoE. While PPIs are conditionally recommended with limited evidence, TCS is strongly recommended with more substantial evidence over no treatment. Oesophagal dilations were conditionally recommended with low certainty evidence to improve symptoms but not histology with oesophagal eosinophilic inflammation.

It is important to note that the guideline acknowledges the limitations of the available evidence, as most studies have relied on single-arm observational designs or historical placebo groups.

Furthermore, the guideline discusses the role of oesophagal dilations, which are conditionally recommended to improve symptoms but not histology in cases of oesophagal eosinophilic inflammation. This intervention is typically performed during endoscopy at the discretion of the gastroenterologist.

With the recent approval of dupilumab, the clinician faces important decisions regarding its usage. While dupilumab could be considered a first-line agent due to its primary indication, the pivotal trials included patients with PPI-refractory disease and previous management attempts. This suggests its potential as step-up therapy only after other treatment options have been trialled.

Criteria to Consider Initiating Dupilumab

This expert opinion takes into consideration established paradigms for the use of dupilumab in atopic diseases and the general approach of utilising systemic biologic therapy as a last resort for patients who have shown poor responsiveness to standard treatments.

Biologic therapies are relatively newer and more expensive options that payers may not prefer. Additionally, the broad and systemic immune modulatory effects of biologics require careful consideration, as long-term safety and efficacy data may be limited.

It is important to evaluate each patient's specific circumstances, treatment history, and response to previous therapies before considering the use of dupilumab. By carefully assessing these factors, clinicians can make informed decisions regarding the initiation of this novel therapy for optimal patient outcomes.

The guideline then provides contexts where the first-line use of dupilumab should be considered and contexts to consider it as step-up therapy as well as the currently approved use of the medication.

A Shared Decision-Making Approach to Eosinophilic Oesophagitis Treatment

Shared decision-making (SDM) plays a crucial role in the successful treatment of eosinophilic esophagitis (EoE), facilitating a collaborative and informed discussion between patients (or their families) and clinicians.

This process involves exploring the risks, benefits, alternatives, and individual preferences related to EoE treatment options. While SDM has been extensively studied in various medical conditions, there is limited research specific to EoE therapy.

Key elements of SDM include understanding the available evidence and outcomes associated with different treatment decisions, being aware of all potential management options, and providing patients and their families with the opportunity to express their values and preferences.

By incorporating these components, patients can make fully informed decisions aligned with their goals and personal treatment priorities rather than solely relying on clinician recommendations.

The guidelines provide an example matrix for considering EoE therapies in this paradigm and example patient scenarios to varying options as first-time therapies. It covers price and cost-effectiveness, therapy monitoring and future research directions.

Conclusions

In conclusion, this guidance suggests that dupilumab can be considered as a first-line therapy for patients with multiple atopic diseases, even if they do not strictly meet the criteria for other approved indications.

The decision to use dupilumab can be made through SDM after considering other treatment options. For patients with severe EoE, dupilumab can also be considered as a first-line therapy.

Additionally, dupilumab can be used as a step-up therapy for patients who have not responded to other medical or dietary treatments, following a similar approach used in asthma and atopic dermatitis.

It is important to conduct endoscopies and monitor symptoms after initiating dupilumab to evaluate its effectiveness and assess treatment outcomes.

Ongoing clinical experience and trials will provide further insights into the optimal use of dupilumab and other emerging therapeutic approaches.

Read the full publication 

Note: Global access to dupilumab varies, for example, dupilumab has been approved for use in EoE but not in the UK.

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