Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents With Eosinophilic Esophagitis

Swallowed topical corticosteroids have been used off-label for treating eosinophilic esophagitis (EoE) in pediatric patients for some time. Despite their widespread use, there was no FDA-approved swallowed topical corticosteroid available at the time of this study. Budesonide oral suspension (BOS) represents a novel formulation of topical corticosteroid, designed as a viscous suspension to optimize residency time in the esophageal mucosa. Two randomized, double-blind, placebo-controlled phase 2 and phase 3 clinical trials were conducted in adolescents and adults with EoE to evaluate the safety and efficacy of BOS. This study pooled data specifically from adolescents enrolled in both trials to assess the safety and efficacy in this age group.This study analyzed patients with EoE from the following clinical studies: phase 2 (MPI 101-06; Clinical- Trials.gov identifier: NCT01642212) and phase 3 (SHP621-301; ClinicalTrials.gov identifier: NCT02605837). Key inclusion criteria included: patients aged 11 to 17 years with confirmed diagnosis of EoE, (peak eosinophil count ≥ 15 eos/hpf at ≥2 esophageal levels), that did not respond to high-dose proton pump inhibitor therapy for ≥6 weeks, and presence of dysphagia symptoms. Criteria for exclusion included: concomitant treatment with immunomodulators, other swallowed topical corticosteroids or systemic corticosteroids; presence of a high-grade esophageal stricture; or following a 6-food elimination or a pure liquid diet.A pooled post hoc analysis was performed from data of adolescents from 2 multicenter, 12 week, double-blind, and placebo-controlled trials. During the screening portion, patients underwent upper endoscopy with biopsies, which was then followed by symptom assessment for 4 weeks. Afterward, eligible patients were randomized to BOS 2.0 mg twice daily or placebo for up to 12 weeks. The primary efficacy endpoints included proportion of patients who achieved histologic responses (≤1, ≤6, and <15 eos/hpf at all esophageal levels), dysphagia symptom response (≥30% reduction in DSQ score from baseline), and clinicopathologic response (≤6 eos/hpf and ≥30% reduction in DSQ score) at week 12 of therapy. Additional efficacy endpoints, such as changes in endoscopic findings, were also assessed. Safety assessments included adverse event monitoring, dual x-ray absorptiometry for bone mineral density, and ACTH stimulation testing.Seventy-six patients (aged 11–17 years) were randomized to BOS (n = 45) or placebo (n = 31). BOS-treated patients showed higher rates of histologic remission compared with those who received placebo: 42.2% versus 0.0% with ≤1 eos/hpf, 46.7% versus 6.5% achieved remission with ≤6 eos/hpf, and 53.3% versus 9.7% with <15 eos/hpf. There was also a higher dysphagia symptom response in the BOS group (68.9% versus 58.1%), though this was not statistically significant. Additionally, BOS resulted in a higher clinicopathologic response rate (31.1% versus 3.2%) compared with placebo, defined as a combined histologic and dysphagia symptom response (≤6 eos/hpf and ≥30% reduction in DSQ score from baseline) and the least-squares mean of the change in peak eosinophil counts, EoE Histology Scoring System total score ratios (grade [severity] and stage [extent]). BOS-treated patients also had greater improvements in peak eosinophil counts, EoE Histology Scoring System total score ratios, and total EoE Endoscopic Reference Scores from baseline to week 12. Overall, BOS was well-tolerated with no significant difference in all categories of adverse events compared with placebo.After 12 weeks of BOS therapy, adolescent patients with EoE showed significant histologic and clinicopathologic improvements compared with those receiving placebo. Although there was a numerical improvement in dysphagia symptom response, it did not reach statistical significance. Overall, BOS therapy was well tolerated.Managing EoE presents significant challenges given the limited treatment options available. Dietary restrictions in our pediatric population can be quite challenging. Moreover, although off-label use of swallowed topical steroids has shown efficacy in this condition, their potential impact on pediatric growth and development necessitates careful consideration, prompting exploration of more targeted approaches like BOS. This study demonstrated safety and improved efficacy of BOS 2.0 mg twice daily compared with placebo in adolescents. This study’s main limitation is that it constitutes a post hoc analysis of aggregated data from 2 distinct clinical trials, rather than a dedicated primary trial tailored specifically for the pediatric population. Moreover, the study’s focus solely on the adolescent population excludes a significant portion of younger pediatric EoE patients. Thus, although providing valuable insights into BOS as a novel treatment of adolescents with EoE, this study underscores the necessity for future research that comprehensively includes the entire pediatric population.