@article{1a7e451f6c194885b350dfaf57c3437c,
title = "Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension",
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.)",
keywords = "Dysphagia, Maintenance Therapy, Randomized Treatment Withdrawal",
author = "{ORBIT2/SHP621-302 Investigators} and Dellon, {Evan S.} and Collins, {Margaret H.} and Katzka, {David A.} and Mukkada, {Vincent A.} and Falk, {Gary W.} and Robin Morey and Bridgett Goodwin and Eisner, {Jessica D.} and Lan Lan and Desai, {Nirav K.} and James Williams and Ikuo Hirano and Curtis Baum and Pradeep Bekal and David Chaletsky and Mirna Chehade and Larry Clark and Evan Dellon and Reed Dimmitt and David Dulitz and Gary Falk and Ronald Fogel and Keith Friedenberg and Scott Gabbard and Andrew Gentry and Benjamin Gold and Michael Goldstein and Sandeep Gupta and Karen Hsu-Blatman and Vikram Jayanty and David Katzka and Vidhya Kunnathur and John Lee and John Leung and Jonathan Markowitz and Calies Menard-Katcher and Benjamin Mitlyng and Moussa, {Sam E.} and Vincent Mukkada and Molly O'Gorman and Juan Olazagasti and Timothy Ritter and Wael Sayej and Shauna Schroeder and Yamen Smadi and Daniel Soteres and Theodore Stathos and Vaezi, {Michael F.} and Tom Whitlock and John Wo",
note = "Funding Information: Funding This study was funded by Shire ViroPharma, Inc , a member of the Takeda group of companies. Medical writing support was provided by Joanna L. Donnelly, PhD, of PharmaGenesis London, London, UK, and was funded by Takeda Pharmaceuticals USA, Inc . Funding Information: Funding This study was funded by Shire ViroPharma, Inc, a member of the Takeda group of companies. Medical writing support was provided by Joanna L. Donnelly, PhD, of PharmaGenesis London, London, UK, and was funded by Takeda Pharmaceuticals USA, Inc. Conflicts of interest The authors disclose the following: Evan S. Dellon has received research funding from Adare Pharmaceuticals, Allakos, AstraZeneca, GlaxoSmithKline, Meritage Pharma, Inc, Miraca Life Sciences, Nutricia, Receptos/Celgene, Regeneron Pharmaceuticals, and Shire, a Takeda Company, and is a consultant for Abbott Laboratories, Adare Pharmaceuticals, Aimmune Therapeutics, Allakos, Amgen, Arena Pharmaceuticals, AstraZeneca, Biorasi, Calypso Biotech, Celldex Therapeutics, Inc, EsoCap Biotech, GlaxoSmithKline, Gossamer Bio, Lilly, Parexel/Calyx Clinical Trial Solutions, Receptos/Celgene, Regeneron Pharmaceuticals, Robarts Clinical Trials, Inc/Alimentiv, Inc, Salix Pharmaceuticals, Sanofi, and Shire, a Takeda Company, and has received educational grants from Allakos, Banner Life Sciences, and Holoclara; Margaret H. Collins has received research funding from Meritage Pharma, Inc, Receptos/Celgene, Regeneron Pharmaceuticals, and Shire, a Takeda Company, and is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene, Regeneron Pharmaceuticals, Robarts Clinical Trials, Inc/Alimentiv, Inc, and Shire, a Takeda Company; David A. Katzka has received research funding from Shire, a Takeda Company, and a consulting fee from Receptos/Celgene; Vincent A. Mukkada has received research funding from Meritage Pharma, Inc, and Shire, a Takeda Company, and is a consultant for Shire, a Takeda Company; Gary W. Falk has received research funding from Adare Pharmaceuticals, Allakos, Lucid, Receptos/Celgene, Regeneron Pharmaceuticals, and Shire, a Takeda Company, and is a consultant for Adare Pharmaceuticals, Allakos, Bristol Myers Squibb, Lucid, Regeneron Pharmaceuticals, and Shire, a Takeda Company; Robin Morey, Bridgett Goodwin, Nirav K. Desai, and James Williams are employees of Takeda Development Center Americas, Inc, and stockholders of Takeda Pharmaceutical Company Limited; Jessica D. Eisner was an employee and stockholder of Takeda Pharmaceuticals USA, Inc, and a stockholder of Takeda Pharmaceutical Company Limited, at the time of the study; Lan Lan was an employee of Takeda Development Center Americas, Inc, and a stockholder of Takeda Pharmaceutical Company Limited, at the time of the study; and Ikuo Hirano has received research funding from Adare Pharmaceuticals, Allakos, Arena Pharmaceuticals, AstraZeneca, Meritage Pharma, Inc, Receptos/Celgene, Regeneron Pharmaceuticals, and Shire, a Takeda company, and is a consultant for Adare Pharmaceuticals, Allakos, Arena Pharmaceuticals, AstraZeneca, EsoCap Biotech, Gossamer Bio, Lilly, Meritage Pharma, Inc, Receptos/Celgene, Regeneron Pharmaceuticals, and Shire, a Takeda Company. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = jul,
doi = "10.1016/j.cgh.2021.06.020",
language = "English",
volume = "20",
pages = "1488--1498.e11",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "7",
}