What is Dupixent (dupilumab) and can it be used to treat eosinophilic esophagitis (EoE)?

What is Dupixent and Can It Be Used for EoE?

Dupixent (dupilumab) is now FDA-approved for treating eosinophilic esophagitis in patients aged 1 year and older weighing at least 15 kg, making it a definitive treatment option for this condition. 1

What is Dupixent?

Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor-α, thereby inhibiting signaling of both interleukin-4 and interleukin-13—two cytokines central to type 2 inflammatory conditions. 2

The drug is FDA-approved for multiple atopic conditions including:

• Atopic dermatitis (ages 6 months and older) 1
• Moderate-to-severe asthma with eosinophilic phenotype (ages 6 years and older) 1
• Chronic rhinosinusitis with nasal polyps (ages 12 years and older) 1
• Eosinophilic esophagitis (ages 1 year and older, weighing ≥15 kg) 1
• Prurigo nodularis, COPD with eosinophilic phenotype, chronic spontaneous urticaria, and bullous pemphigoid (adults) 1

FDA-Approved Use for EoE

Dupilumab is definitively approved for EoE treatment, representing a major advancement beyond the 2020 guideline recommendations that limited its use to clinical trials only. 1 The 2020 AGA/Joint Task Force guidelines recommended using anti-IL-4 receptor-α therapy only in clinical trial contexts due to limited data at that time. 3

Evidence Supporting Dupilumab in EoE

Efficacy in Adults and Adolescents

In the phase 3 LIBERTY EoE TREET trial, dupilumab 300 mg weekly achieved histologic remission (≤6 eosinophils/hpf) in 59-60% of patients versus only 5-6% with placebo at week 24. 2

• Mean dysphagia scores improved significantly with weekly dupilumab compared to placebo, with differences of -9.92 to -12.32 points on the Dysphagia Symptom Questionnaire. 2
• Improvements in histologic, endoscopic, and symptomatic measures were maintained through week 52. 2
• Dupilumab was effective regardless of prior treatment failures with swallowed topical corticosteroids, food elimination diets, or esophageal dilation. 4

Efficacy in Children

In children aged 1-11 years, dupilumab achieved histologic remission in 58-68% of patients versus 3% with placebo at week 16. 5

• The higher-exposure regimen demonstrated significant improvements across histologic, endoscopic, and transcriptomic measures. 5
• Improvements were sustained through week 52 in the extension phase. 5

Real-World Evidence

Real-world data demonstrates that patients treated with dupilumab for other atopic conditions who had concomitant EoE experienced dramatic improvement in their esophageal disease. 6, 7

• In a retrospective review of 45 patients, 22 of 26 with follow-up histology achieved <6 eosinophils/hpf after dupilumab initiation (mean reduction from 52.9 to 4.5 eos/hpf). 6
• Twenty-four of 28 patients reported complete symptom resolution. 6
• Twenty-nine patients were able to reduce or discontinue EoE-directed therapies (swallowed steroids, PPIs) or expand their diets. 6

Clinical Response Timeline

Symptomatic improvement begins as early as week 4, with significant dysphagia reduction by week 10. 8

Histologic remission is typically assessed at 16-24 weeks, aligning with standard EoE treatment evaluation protocols. 8

Endoscopic improvements become evident by weeks 12-24. 8

Critical Caveat

Despite symptomatic improvement, endoscopic confirmation with biopsies remains essential at 8-12 weeks, as 41% of EoE patients may report symptomatic response without achieving histological remission. 8

Dosing for EoE

For patients aged 1 year and older weighing ≥15 kg, dupilumab is administered subcutaneously with weight-tiered dosing. 1

• The medication is given as a subcutaneous injection into the thigh, abdomen (avoiding 2 inches around the navel), or upper arm (if administered by a caregiver). 1
• Injection sites should be rotated with each dose. 1

Safety Considerations

Serious adverse events occurred in approximately 5-7% of patients receiving dupilumab in clinical trials. 2, 5

• Common adverse events (≥10 percentage points higher than placebo) included COVID-19, nausea, injection-site pain, and headache in pediatric trials. 5
• No significant safety signals emerged that would preclude use in EoE. 2

Comparison to Guideline Recommendations

The 2020 AGA guidelines recommended against using dupilumab outside clinical trials due to preliminary data at that time. 3 The guidelines noted that while a phase 2 study showed promise with dupilumab demonstrating symptom, histologic, and endoscopic efficacy in 47 adults, full publication was not available for systematic review. 3

The subsequent FDA approval based on robust phase 3 data supersedes these earlier guideline limitations, establishing dupilumab as a standard treatment option for EoE. 1, 2, 5

Clinical Algorithm for Dupilumab Use in EoE

Consider dupilumab for:

• Patients with confirmed EoE (≥15 eosinophils/hpf) who are aged ≥1 year and weigh ≥15 kg 1
• Patients who have failed or cannot tolerate swallowed topical corticosteroids 4
• Patients with multiple atopic comorbidities (atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps) 6, 7
• Patients requiring long-term maintenance therapy 2

Initiate therapy with weight-appropriate dosing per FDA label, assess symptomatic response at 4-10 weeks, and confirm histologic remission with endoscopy and biopsies at 16-24 weeks. 8, 1, 2