Abstract
Background & Aims: We aimed to determine the safety and efficacy of budesonide oral suspension (BOS) maintenance therapy in patients with eosinophilic esophagitis (EoE). Methods: We performed an open-label extension study of a 12-week, multicenter, randomized, double-blind, placebo-controlled trial. Patients with EoE (11–40 years old) who completed double-blind BOS (n = 45) or placebo therapy (n = 37) received 24 weeks’ open-label BOS (2.0 mg once daily for 12 weeks, with optional dose increase [1.5–2.0 mg twice daily] for 12 weeks thereafter). Predefined efficacy outcomes included: proportion of patients with a histologic response (≤6 eosinophils/high-power field [eos/hpf]) and change in mean peak eosinophil counts after 24 weeks. Analyses were stratified by patients who received placebo (placebo/BOS) or BOS (BOS/BOS) during the double-blind trial. Results: BOS was well tolerated and drug-related adverse events were uncommon (placebo/BOS, 19% [7/37]; BOS/BOS, 4% [2/45]). Incidence of oral candidiasis (1 per group) and esophageal candidiasis (placebo/BOS group, n = 4) remained low. Changes in morning serum cortisol levels were not clinically relevant. A histologic response was observed in 49% (16/33) of patients receiving placebo/BOS and 23% (9/39) receiving BOS/BOS. Mean peak eosinophil counts (baseline vs week 24 or early termination) were: placebo/BOS, 118.8 vs 29.1; P <.001 and BOS/BOS, 38.1 vs 72.4; P =.01. Of the patients who responded to double-blind therapy, 42% maintained a histologic response during the open-label extension; 4% of nonresponders gained response. Conclusions: In an open-label extension study of patients with EoE, BOS was well tolerated and drug-related adverse events were uncommon. BOS maintained a histologic response in some initial responders, but few initial nonresponders had a response. ClinicalTrials.gov no: NCT01642212.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 666-673.e8 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 17 |
| Issue number | 4 |
| DOIs | |
| State | Published - Mar 2019 |
Funding
The authors thank all MPI-101-06 investigators (listed in the Supplementary Material ) and participants for their contribution to this study. The authors thank Mohamed Hamdani of Shire, who previously provided statistical support for this study. They also thank Luci Witcomb, PhD, of PharmaGenesis London, for providing medical writing support funded by Shire International GmbH . Conflicts of interest The authors disclose the following: Evan S. Dellon has received research funding from Meritage, Miraca Life Sciences, Nutricia, Receptos, Regeneron, and Shire; is a consultant for Adare Pharmaceuticals, Alivio Therapeutics, Banner Life Sciences, Enumeral, GlaxoSmithKline, Receptos, Regeneron, and Shire; and has received an educational grant from Banner Life Sciences. David A. Katzka has received research funding from Meritage. Margaret H. Collins has received research funding from Biogen Idec., Meritage, Receptos, Regeneron, and Shire. Sandeep K. Gupta has received research funding from Meritage; and is a consultant for Meritage and Receptos. Lan Lan and James Williams are employees and stockholders of Shire. Ikuo Hirano has received research funding from Meritage, Receptos, Regeneron, and Shire; and is a consultant for Meritage, Receptos, Regeneron, and Shire. The authors thank all MPI-101-06 investigators (listed in the Supplementary Material) and participants for their contribution to this study. The authors thank Mohamed Hamdani of Shire, who previously provided statistical support for this study. They also thank Luci Witcomb, PhD, of PharmaGenesis London, for providing medical writing support funded by Shire International GmbH. Conflicts of interest The authors disclose the following: Evan S. Dellon has received research funding from Meritage, Miraca Life Sciences, Nutricia, Receptos, Regeneron, and Shire; is a consultant for Adare Pharmaceuticals, Alivio Therapeutics, Banner Life Sciences, Enumeral, GlaxoSmithKline, Receptos, Regeneron, and Shire; and has received an educational grant from Banner Life Sciences. David A. Katzka has received research funding from Meritage. Margaret H. Collins has received research funding from Biogen Idec., Meritage, Receptos, Regeneron, and Shire. Sandeep K. Gupta has received research funding from Meritage; and is a consultant for Meritage and Receptos. Lan Lan and James Williams are employees and stockholders of Shire. Ikuo Hirano has received research funding from Meritage, Receptos, Regeneron, and Shire; and is a consultant for Meritage, Receptos, Regeneron, and Shire. Funding Meritage Pharma, Inc., now a part of the Shire group of companies, contributed to the design and conduct of the study; collection and management of the data; and reviewed the manuscript for medical accuracy. Approval of the manuscript, and the decision to submit the manuscript for publication, was the responsibility of the authors.
Keywords
- Clinical Trial
- Corticosteroid
- Esophagus
- Treatment
ASJC Scopus subject areas
- Hepatology
- Gastroenterology
