Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension
Evan S. Dellon, Margaret H. Collins, David A. Katzka, Vincent A. Mukkada, Gary W. Falk, Robin Morey, Bridgett Goodwin, J Eisner, Lan Lan, Nirav K. Desai, J. E. Williams, Ikuo Hirano, Curtis A. Baum, Pradeep Bekal, David M. Chaletsky, Mirna Chehade, Larry Clark, Evan S. Dellon, Reed A. Dimmitt, David Dulitz, Gary W. Falk, Ronald Fogel, Keith Friedenberg, Scott Gabbard, Andrew Donald Gentry, Benjamin D. Gold, Michael Goldstein, Sandeep K. Gupta, Ikuo Hirano, Karen Hsu-Blatman, Vikram Jayanty, David A. Katzka, Vidhya Kunnathur, John Lee, John Leung, Jonathan E. Markowitz, Calies Menard‐Katcher, Benjamin Mitlyng, Sam E. Moussa, Vincent A. Mukkada, Molly O’Gorman, Juan C. Olazagasti, Timothy Ritter, Wael N. Sayej, Shauna Schroeder, Yamen Smadi, Daniel Soteres, Theodore H. Stathos, Michael F. Vaezi, Tom L. Whitlock, John M. Wo, Ziad Younes, Salam Zakko
Abstract
BACKGROUND & AIMS: We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study. METHODS: Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes. RESULTS: The randomized withdrawal period enrolled 48 patients (BOS-BOS, n = 25; BOS-PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns. CONCLUSIONS: For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).