Professionals

Authors
Laserna-Mendieta EJ, Úbeda-Vargas V, et al.

Journal
Am J Gastroenterol 2026. Published online June 24, 2026.

Paper of the Month – Selected and discussed by Christoph Schlag

🎯 Study Aim

While the pivotal trials (LIBERTY EoE TREET) established dupilumab's efficacy in eosinophilic esophagitis (EoE) under controlled trial conditions, large prospective real-world data were lacking — particularly on flexible dosing regimens and on patients with a fibrostenotic phenotype, who were largely excluded from the registration trials.

🔬 Methods

Cross-sectional analysis from the EoE CONNECT registry (the largest European multicenter EoE database, maintained by EUREOS), which prospectively collects patient data from 22 centers in Spain, Italy, and Denmark. A total of 161 patients (145 adults, 16 adolescents) receiving dupilumab outside of clinical trials were included.

📊 Key Findings

• The cohort was clinically complex: 69% showed endoscopic fibrotic features (rings/strictures) at diagnosis, and 37.5% had a mixed or stricturing phenotype.
• After a median of 6.5 months, peak eosinophil count dropped from 57 ± 45 to 8 ± 19 eos/hpf, the Dysphagia Symptom Score (DSS) improved from 5.8 ± 3.7 to 2.5 ± 2.8, and the endoscopic reference score (EREFS: edema, rings, exudates, furrows, strictures) improved from 3.0 ± 1.6 to 1.3 ± 1.3 (all p < 0.001).
• Clinico-histological response (CHR, combining clinical and histological criteria) was achieved by 86.0% on weekly 300 mg dosing and 81.2% on semiweekly dosing — no significant difference (p = 0.57), and improvements in eosinophil counts, EREFS, and DSS were all comparable between the two regimens.
• The strongest predictor for choosing the less frequent (semiweekly) regimen was severe concomitant atopy as the reason for starting dupilumab (OR 26.9; p < 0.001)
• Dose adjustments worked well: de-escalation from weekly to semiweekly succeeded in all evaluable patients (8/8) while maintaining CHR; escalation from semiweekly to weekly rescued 80% (4/5) of initial non-responders.
• Discontinuation rate was low at 5% (mainly due to tolerability issues such as arthralgia/myalgia and injection-site pain); adverse events were generally mild and rarely led to treatment cessation.

🧠 Interpretation

The study confirms that the efficacy demonstrated in pivotal trials — including meaningful endoscopic healing, not just histological and symptomatic improvement — translates well into everyday clinical practice, even in patients with advanced, fibrostenotic disease who might otherwise be considered primarily for endoscopic dilation. It also provides the first robust real-world evidence that a semiweekly dosing regimen can be a similarly effective — and potentially more cost-effective — alternative to the approved weekly standard dose in selected patients (particularly those with relevant atopic comorbidity), and that individualized dose adjustments (escalation/de-escalation) are a practical management tool.

⚠️ Critical Appraisal

Cross-sectional design with variable follow-up intervals, potential selection bias (dupilumab often reserved for severe/refractory cases), and no control group.