Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with increasing incidence in all age groups^1,2 and limited treatment options for pediatric patients. We evaluated the efficacy and safety of two doses of a novel budesonide oral suspension (BOS) for induction therapy of pediatric EoE in a phase 2/3 trial.

Aims & Methods

An initial 12-week randomized, double-blind (DB) induction phase enrolled 76 pediatric patients with active EoE aged 2-11 years (stratum I; n=35) and 12-17 years (stratum II; n=41). Patients were randomized to high-dose BOS (BOS-H: 0.5 mg (stratum I)/1 mg (stratum II) BOS, twice daily; n=26), low-dose BOS (BOS-L: 0.5 mg (stratum I)/1 mg (stratum II) BOS, once daily; n=26) or placebo (n=24). The composite primary endpoint was the proportion of patients with histologic remission plus clinical response at week 12. Secondary endpoints included the proportion of patients with histologic remission, change in peak eosinophil counts, and the proportion of patients with clinical response. Patients who did not achieve the primary endpoint at week 12, who experienced a food impaction requiring endoscopic intervention or dilation, or with a lack of efficacy after week 8 were eligible for a subsequent open-label induction (OLI) phase. In this additional phase, 45 patients all received BOS-H for a further 12 weeks, after which the same endpoints were assessed.

Results

In the DB phase, the proportion of patients achieving the composite endpoint of histologic remission plus clinical response was significantly higher in both BOS treatment groups compared with placebo, with superior and clinically relevant results with high-dose versus low-dose BOS (Table). Both BOS doses demonstrated significantly superior benefits versus placebo on the secondary endpoints of histologic remission and peak eosinophil counts. However, no relevant differences were observed in clinical response between any groups. In the OLI phase, patients who received BOS-L or placebo in the DB phase achieved comparable rates of histologic remission and clinical response as the BOS-H group in the DB phase (Table).
Esophageal candidiasis was observed in 1 patient receiving BOS-H in the DB phase and 4 patients in the OLI phase. Decreased cortisol levels were recorded in 1 BOS-H patient, 1 placebo patient, and 1 OLI patient, with 1 case each of adrenal insufficiency and adrenal suppression in the OLI phase. Adrenal-related events were of mild severity. No bolus impactions requiring emergency endoscopy or serious adverse events related to BOS were reported.

Efficacy endpoints (full analysis set):

Conclusion

BOS was safe and effective in inducing histologic remission associated with clinical response in pediatric patients with EoE. Superiority of BOS on the primary clinico-histologic endpoint and secondary histologic endpoints was demonstrated over placebo and for high-dose versus low-dose BOS. Clinical response rates were comparable among treatment groups. Treatment with high-dose BOS for a further 12 weeks led to improvement in patients not achieving remission in the DB phase. Adverse events were of mild or moderate severity.

References

1 Navarro P, Arias Á, Arias-González L, Laserna-Mendieta EJ, Ruiz-Ponce M, Lucendo AJ. Systematic review with meta-analysis: the growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther. 2019;49(9):1116-1125.

2 Roberts SE, Morrison-Rees S, Thapar N, Williams JG. Incidence and prevalence of eosinophilic oesophagitis across Europe: A systematic review and meta-analysis. United European Gastroenterol J. 2024;12(1):89-102.

Disclosure

Alfredo J. Lucendo: Consulting fees from Dr. Falk, Esocap; research support from Arena, AstraZeneca, Dr. Falk, EsoCap, Regeneron, Sanofi.
Alexandra Papadopoulou: Speaker and consulting fees from Adare, Cross, Dr. Falk, Danone (Nutricia), Nestle, Petsiavas, Sanofi, Specialty Therapeutics, Touch Independent Medical Education, Uni-Pharma Pharmaceutical Laboratories; research support from Abbvie, AstraZeneca, Dr. Falk, Takeda, United Pharmaceuticals.
Marcus Karl-Heinz Auth: Consulting fees from Dr. Falk; research support from GutsUK/BSPGHAN; travel support from Abbott, Danone (Nutricia), and RD.
Johanna C. Escher: Consulting fees from Abbvie, Janssen; education support from Abbvie; research support from MSD.
Michiel van Wijk: Speaker fees from Danone (Nutricia).
Gloria Dominguez-Ortega: Consulting fees from RD (Mead Johnson Nutrition); education support from Nestle Health Service, Danone (Nutricia).
Noam Zevit: Speaker fees from Rafa, Regeneron, Sanofi; consulting fees from AstraZeneca, Rafa, Regeneron, Sanofi.
Vassiliki-Maria Karagianni: Research support from AstraZeneca, Dr. Falk, Takeda.
Maria Rogalidou: Research support from AstraZeneca, Takeda, United Pharmaceuticals; speaker fees and travel support from Danone (Nutricia), Nestle.
Michael Vieth: Speaker fees from Abbvie, Dr. Falk, Eli Lilly, Malesci.
Jorge Amil-Dias: Speaker fees from Capricare, Danone, Ferrer, Takeda; consulting fees from Adacyte.
Sarah Burrack, Ralph Mueller, Roland Greinwald: Employees of Dr. Falk Pharma GmbH.