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

BACKGROUND & 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 2 preceding phase 3 studies. On the basis of 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 were 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. CONCLUSIONS: 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. CLINICALTRIALS: gov number: NCT03245840.