The role of dupilumab in the treatment of eosinophilic esophagitis

Abstract

Dupilumab has been approved to treat a variety of atopic disorders and was the first US FDA-approved medication for the treatment of eosinophilic esophagitis (EoE), initially approved in May 2022, with expansion in use to patients as young as 1 year of age weighing at least 15 kg in January 2024. It is a fully human monoclonal antibody that inhibits both IL-4 and IL-13 signaling, suppressing TH2-mediated proinflammatory cytokines, chemokines and IgE implicated in EoE pathogenesis. Phase II and III trials in EoE have demonstrated histologic, endoscopic and symptomatic improvement in disease activity with an overall favorable safety profile. This article will review the available clinical trial data and real-world efficacy of dupilumab in EoE.

Plain language summary

Dupilumab is a biologic medication used for the treatment of eosinophilic esophagitis. Clinical trials have shown that this medication is effective in treating both inflammation in the esophagus and symptoms associated with eosinophilic esophagitis in a high proportion of patients. Dupilumab was well tolerated by the majority of clinical trial patients, though side effects such as injection site redness and swelling have been reported. More serious side effects are overall rare.

Article highlights

Background

• Dupilumab is a fully humanized monoclonal antibody. It acts on the IL-4α subunit shared by both IL-4 and IL-13 receptors. By blocking these receptors, dupilumab inhibits both IL-4 and IL-13 signaling, suppressing TH2-mediated proinflammatory cytokines, chemokines and IgE that are involved in many atopic conditions.

• Dupilumab has been approved to treat a variety of atopic disorders, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, prurigo nodularis and eosinophilic esophagitis (EoE).

• Dupilumab is administered subcutaneously. Dosing and interval of administration depends in part on age, weight and indication, ranging from 200 mg monthly to 300 mg weekly.

Clinical efficacy

• The LIBERTY EoE TREET study, the Phase III clinical trial looking at efficacy and safety of dupilumab in patients 12 years and older with active EoE demonstrated 60% of participants receiving weekly dupilumab achieved histologic remission as compared with 5% with placebo (p < 0.001) at 24 weeks.

• EoE KIDS Phase III clinical trial evaluating efficacy of dupilumab in children ages 1–11 years demonstrated that 68% of patients receiving higher-exposure dupilumab achieved histologic remission (defined as <6 eos/hpf), along with significant improvements in histologic, endoscopic and transcriptomic measures as compared with placebo at 16 weeks, with similar improvements seen up to 52 weeks.

Safety & tolerability

• Dupilumab has a favorable long-term safety and adverse effect profile. The most common reported adverse event for dupilumab is injection site reaction (18%). Other common adverse events included nasopharyngitis, exacerbation of atopic dermatitis, upper respiratory tract infections oral herpes, conjunctivitis and headaches.

Keywords: :

• biologics
• dupilumab
• eosinophilic esophagitis
• IL-13
• IL-4
• TH2

Author contributions

All authors contributed to the conception of the work, drafting the work or reviewing it critically for important intellectual content and were involved in final approval of the version to be published.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Competing interests disclosure

The author’s institution is a study site for phase 3 trials entitled “A randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of dupilumab in pediatric patients with active eosinophilic esophagitis” sponsored by Sanofi and Regeneron Pharmaceuticals. EP Syverson acted as a consultant on a medical advisory board sponsored by Sanofi. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.