Long-Term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: a 4-Year, Phase 3, Open-Label Study.

Abstract

Background and aims: We investigated the long-term safety and efficacy of budesonide oral suspension (BOS) in eosinophilic esophagitis (EoE).

Methods: This study (SHP621-303) was a 4-year, phase 3, open-label study in patients with EoE who completed up to 52 weeks of BOS therapy in two preceding phase 3 studies. Based on treatment assignments in previous studies, patients were assigned to BOS-BOS or placebo-BOS groups. All patients received BOS 2.0 mg twice daily; dose reductions to once daily and interruptions were permitted. The safety and tolerability of BOS was primarily investigated, with exploratory efficacy endpoints also examined.

Results: Overall, 131 patients were included. BOS was well tolerated, with no unexpected safety signals observed. Treatment-emergent adverse events (TEAEs) occurred in 76.3% of patients; most were mild/moderate in severity and unrelated to study drug. The most frequently reported BOS-related TEAEs included abnormal adrenocorticotropic hormone stimulation test results (8.4% [11/131]; number of events [m] = 12) and adrenal insufficiency (2.3% [3/131]; m = 3). Esophageal candidiasis occurred in 3.1% of patients ([4/131]). The aforementioned TEAEs resolved in most patients. At month 48 of treatment, 50.0% and 58.3% of patients achieved/maintained a histologic response (≤6 and <15 eosinophils per high-power field, respectively). The initial reduction (-3.6) in total EoE Endoscopic Reference Score from baseline to the first visit was maintained until month 48.

Conclusion: Long-term treatment with BOS was well tolerated. Despite dosing changes/interruptions, approximately half of patients achieved/maintained a histologic response; initial improvements in endoscopic outcomes were maintained over 48 months.