As part of the Pediatric Eosinophilic Esophagitis Research Study, researchers from Meritage Pharma and Indiana and Cincinnati Universities investigated the safety and efficacy of oral budesonide suspension (OBS) therapy of eosinophilic esophagitis (EoE). Children aged 2–18 years with at least 20 eosinophils per high-power field (HPF) on biopsy in multiple levels of the esophagus and symptoms consistent with EoE (based on an unvalidated symptom survey) were recruited from 16 centers, and were randomized to receive either placebo or OBS (at low, medium, or high dose). Participants were treated for 12 weeks, weaned from study medication over 3 weeks, and followed up for adverse events (AE) 4 weeks later. Cortisol levels, change in height and blood pressure, and occurrences of oropharyngeal and esophageal candidiasis were assessed to evaluate AE related to corticosteroid usage. The primary outcome was a positive response to therapy, defined as <6 eosinophils per HPF at all levels of the esophagus on post-therapy biopsy, and >50% reduction in symptom score compared to baseline. The percentage of responders in each of the OBS treatment groups was compared to that among placebo recipients using logistic regression.
Eighty-two patients were randomized (approximately 20 per each of the 4 groups), and 71 participants completed the study. Participants in both the medium- and high-dose OBS groups had significantly higher rates of responders compared to the placebo group (52.6%, 47.1%, and 5.6%, respectively; P = .009 for the comparison between the medium-dose OBS and placebo groups, and P = .017 for the comparison of the high-dose OBS and placebo groups). There was no significant difference in rate of responders between those in the low-dose OBS and placebo groups. However, histologic response rates appeared to be dose-dependent: approximately 6%, 24%, 53%, and 94% for placebo, low-, medium-, and high-dose OBS, respectively. There was a large symptomatic response to placebo (78%), which was comparable to the symptomatic response rates among those receiving the OBS.
There were no significant differences in mean cortisol levels among children in each of the groups, though 1 participant receiving the OBS had a transient low cortisol level at the end of the treatment period. No height differences were noted among groups. There was a slight increase in blood pressure among those in the OBS groups compared to placebo, and 2 OBS-treated patients developed oropharyngeal or esophageal candidiasis.
The authors conclude that medium- and high-dose OBS is safe and effective in the treatment of EoE.
Drs Herzlinger and Ross have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
- eosinophilic esophagitis
- oral budesonide suspension
EoE is a chronic, allergen-mediated, inflammatory condition affecting the esophagus.1 It typically presents with dysphagia in older children, and nonspecific gastrointestinal complaints in younger children. Diagnosis requires esophageal eosinophilia (>15 eosinophils per HPF) that cannot be explained by other gastrointestinal conditions, such as gastroesophageal reflux disease. Treatment options include dietary eliminations and topical steroids. Prior studies have shown that corticosteroids are effective in treating EoE.2,3 However, they are not approved by the FDA for use in EoE. Instead, typically-inhaled asthma medications are prescribed (off-label) to be swallowed, coating the esophagus to act locally.
The current study is a Meritage Pharma-sponsored Phase 2 clinical trial designed to evaluate the safety and efficacy of a novel, viscous, topically active swallowed formulation of budesonide specifically designed for the treatment of children with EoE. The results show the study medication (OBS) significantly improved histology if taken at sufficient dosing. Virtually all of the participants, including those receiving placebo, had symptomatic improvement over the study period. There was no correlation between reported symptoms and histology. Indeed, the placebo group had the least change in histology but the greatest symptomatic improvement; vice versa for the high-dose OBS group. Thus, patient symptom report is not a valid test for esophageal healing. This finding highlights the need for reliable, noninvasive methods for monitoring EoE patients.
At all doses, OBS appeared to be relatively safe, with only mildly or moderately severe AEs reported. Participants were administered the study medication for 12 weeks, yet patients with EoE require therapy for years. It is notable that only about 50% of patients treated with adequate doses of OBS achieved both a histologic and symptomatic response. Long-term data are still required in order to alleviate concerns about chronic steroid use, including candidiasis, adrenal insufficiency, growth retardation, bone density, and hypertension.
If eventually approved, OBS may be an important option in the treatment of EoE.