BUDESONIDE ORAL SUSPENSION IS EFFECTIVE AND SAFE AS INDUCTION TREATMENT OF EOSINOPHILIC ESOPHAGITIS IN CHILDREN AND ADOLESCENTS: RESULTS FROM THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED INDUCTION PHASE OF A MULTICENTER PEDIATRIC TRIAL (PEDEOS-1)

INTRODUCTION: Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus with increasing incidence in all age groups. Topical corticosteroids are a first line therapy for EoE, however, to date, none have been approved for the EoE treatment in children.

AIMS: To assess the efficacy and safety of two doses of a novel budesonide oral suspension (BOS) compared with placebo for induction of histological remission with clinical response in pediatric patients with active EoE.

METHODS: 76 pediatric patients with active EoE aged 2-11 years (stratum I; n=35) and 12-17 years (stratum II; n=41) were randomly assigned to a high-dose arm (0.5 mg (stratum I)/ 1 mg (stratum II) BOS twice daily [BID]; n=26), a low-dose arm (0.5 mg (stratum I)/ 1 mg (stratum II) BOS once daily [OD]; n=26) or placebo (n=24). The composite primary endpoint was the proportion of patients with both histological remission (peak eos < 16 eos/mm² hpf [<5 eos/hpf]) and clinical response (≥30% decrease in Pediatric Eosinophilic Esophagitis Symptom Severity Module, version 2.0 (PEESS v2.0)) at week 12. Secondary endpoints included: i. Proportion of patients with histological remission; ii. Change in peak eos/mm² hpf; iii. Change in modified endoscopic reference score (EREFS); iv. Proportion of patients with clinical response (as above); v. Proportion of patients with resolution of dysphagia (≤ 2 on a 0–10-point patient numerical rating scale (NRS)).

RESULTS: The proportion of patients achieving the composite endpoint of both histological remission and clinical response was significantly higher for both BOS treatment groups compared with placebo, with the high dose achieving clinically relevant better results than the low dose (Table 1). For histological and endoscopic secondary endpoints, both BOS doses showed statistically superior benefits compared with placebo. However, differences in clinical response could not be demonstrated between BOS and placebo based on PEESS^® v2.0, while dysphagia based on NRS showed a numerical benefit in both BOS groups compared with placebo.
Esophageal candidiasis was observed in a single patient (3.8%) receiving high-dose BOS. Decreased cortisol levels occurred in one patient in the high-dose BOS and one in the placebo group. No bolus impactions requiring emergency endoscopy nor serious adverse events related to BOS or adrenal suppression assessed via ACTH test were reported.

CONCLUSION: BOS was safe and effective in inducing histological remission associated with clinical response in pediatric patients with EoE, with clinically relevant better results obtained in the high dose. Clinical response rates (PEESS v2.0) were comparable among the three groups, although improvement trends in dysphagia resolution could be detected in the two BOS groups. Histological and endoscopic results confirmed the superiority of BOS compared with placebo.