Dupilumab Improves Endoscopic Features in Adult and Adolescent Patients With Eosinophilic Esophagitis: Post Hoc Analysis of LIBERTY EoE TREET Study.

ACG 2025 makes 19 GRADE-rated statements plus non-graded key concepts. DIAGNOSIS: EoE is diagnosed by symptoms of esophageal dysfunction plus at least 15 eos/hpf in at least 1 hpf on esophageal biopsy, after evaluating for non-EoE disorders that cause or potentially contribute to esophageal eosinophilia (strong recommendation, low-quality evidence). A PPI trial is NOT a diagnostic criterion and the term PPI-REE is abandoned; PPIs are positioned purely as a treatment. Obtain at least 6 esophageal biopsies from at least 2 esophageal levels (e.g., proximal/mid and distal), targeting endoscopic findings if possible (strong, low). Use a systematic endoscopic scoring system such as the EoE Endoscopic Reference Score (EREFS) at every endoscopy (strong, low). Quantify eosinophil counts, not merely report them as above threshold, on biopsies from every endoscopy performed for EoE (strong, low), since serial counts gauge anti-inflammatory effect; the guideline notes eosinophil density (~60 eos/mm2) may be preferable for cross-setting comparison but that this has not yet been adopted in practice. Key concept: perform the diagnostic endoscopy off treatment (no dietary restriction and no PPI) to maximize diagnostic sensitivity. TREATMENT, the three anti-inflammatory options do NOT carry equal recommendation strength: swallowed topical steroids are recommended (STRONG, moderate evidence); PPIs are suggested (CONDITIONAL, low); empiric food elimination diet is suggested (CONDITIONAL, low). Because the field lacks comparative efficacy trials, the guideline states the choice among them is individualized to disease characteristics and patient preference within a shared decision-making framework, and advises that a single anti-inflammatory therapy be selected initially. Either fluticasone propionate or budesonide is a reasonable initial topical steroid (conditional, low); options include the FDA-approved budesonide oral suspension, the EMA-approved budesonide orodispersible tablet, and off-label asthma preparations adapted for esophageal delivery. Administer topical steroids after meals or at bedtime with nothing to eat or drink for 30-60 minutes to maximize esophageal dwell time; in young children prefer a slurry/suspension over an inhaler device. Dosing (Table 6): high-dose PPI, adults, double the approved reflux dose per day (e.g., omeprazole 20 mg twice daily or 40 mg daily or PPI equivalent); children, 2 mg/kg/day (or 1 mg/kg twice daily). Budesonide, adults 2-4 mg/day, divisible twice daily (approved budesonide oral suspension dosing is 2 mg twice daily); children 1-2 mg/day by age/height/weight. Fluticasone, adults 1,760 mcg/day in divided doses; children 110-880 mcg/day in divided doses. Currently available allergy testing (skin prick, patch, or serum Ig panels) is NOT suggested to direct elimination diets (conditional, very low). Providers MAY consider starting with a less-restrictive empiric elimination (1FED or 2FED) as the initial diet choice, incorporating patient preference through shared decision-making, and should collaborate with a dietician or nutritionist; after an initial dietary response a structured food reintroduction process is advised, with endoscopy and biopsy after each food reintroduced, because symptoms alone must not be used to determine food triggers. BIOLOGICS: dupilumab is suggested for EoE in individuals 12 years of age or older who are nonresponsive to PPI therapy (conditional, moderate) and, as a separate statement, for pediatric patients aged 1-11 years weighing at least 15 kg who are nonresponsive to PPI therapy (conditional, low). Dosing: 15 to <30 kg, 200 mg subcutaneously every other week; 30 to <40 kg, 300 mg subcutaneously every other week; >=40 kg, 300 mg subcutaneously weekly. Key concept: use dupilumab as step-up therapy in difficult-to-treat patients, and consider it in patients with multiple atopic conditions that would independently meet requirements for its use; the guideline explicitly states its position in the treatment algorithm is still being determined. No recommendation can be made for or against cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. Omalizumab is suggested AGAINST (conditional, low), as are cromolyn and montelukast (conditional, very low). DILATION: endoscopic dilation is suggested as an ADJUNCT to medical therapy for esophageal strictures causing dysphagia (conditional, low). Dilation alone does not affect underlying inflammatory disease activity, so in fibrostenotic EoE it should occur in conjunction with effective medical or dietary anti-inflammatory therapy. Use a start-low-and-go-slow approach: begin with a dilator size that may underestimate esophageal caliber, relook after dilation, and work to larger sizes until a mucosal disruption ('dilation effect') or the target diameter is reached. In adults and adolescents, a goal luminal diameter that relieves dysphagia and food impaction, typically at least 16 mm, should be achieved over one or more sessions, depending on initial luminal caliber and the effect observed during dilation. Dilation technique may be chosen by stricture characteristics and endoscopist preference. MAINTENANCE: continuation of EFFECTIVE dietary or pharmacologic therapy is advised to prevent recurrence of symptoms, histologic inflammation, and endoscopic abnormalities, notably graded STRONG despite low-quality evidence, because disease activity almost universally recurs when treatment is stopped. For patients on pharmacologic treatment, providers should consider identifying the lowest effective dose for long-term use, with any dose-reduction decision individualized. MONITORING AND RESPONSE: evaluate treatment response with symptomatic AND endoscopic AND histologic outcomes (strong, low); providers are advised NOT to monitor symptoms alone, since symptoms do not strongly correlate with endoscopic or histologic disease activity. Perform endoscopy to assess response 8-12 weeks after starting a new therapy such as PPI, topical steroid, or food elimination diet; for dupilumab the assessment interval may range from 12 to 24 weeks based on clinical trial findings. Providers MAY consider using a histologic response threshold of <15 eos/hpf, with the improvement in eosinophil count interpreted in the context of other histologic features, endoscopic findings, and symptoms, the guideline frames this as a 'may consider' key concept rather than a fixed target. Follow-up should be individualized and at shorter intervals for patients with complications (food impaction, perforation, strictures requiring dilation, malnutrition); repeat endoscopy after any treatment change such as dose reduction; care gaps of 2 years or more are associated with progression to fibrostenosis. PEDIATRIC-SPECIFIC: in children with EoE and dysphagia, an esophagram is suggested to evaluate fibrostenotic disease (conditional, very low); evaluation by a feeding therapist and/or dietician is suggested as an adjunctive intervention in children with feeding dysfunction (conditional, very low); growth, development including eating skills, and nutrition are treatment goals in children in addition to symptomatic, endoscopic, and histologic goals.