Gastroenterology

Gastroenterology

Volume 159, Issue 5, November 2020, Pages 1672-1685.e5
Gastroenterology

Original Research
Clinical—Alimentary Tract
Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis

https://doi.org/10.1053/j.gastro.2020.07.039Get rights and content
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Background & Aims

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission.

Methods

We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks.

Results

At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment.

Conclusions

In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029.

Keywords

Topical Corticosteroids
Dysphagia
Remission
Patient-Reported Outcomes

Abbreviations used in this paper

AE
adverse event
BOT
budesonide orodispersible tablet
CI
confidence interval
EoE
eosinophilic esophagitis
EoE-QoL-A
Eosinophilic Esophagitis Quality of Life Scale for Adults
eos/hpf
eosinophils per high-power field
EoT
end of treatment
EREFS
Endoscopic Reference Score
HRQoL
health-related quality of life
NRS
numerical rating scale
PPI
proton pump inhibitor
STC
swallowed topical-acting corticosteroids

Cited by (0)

Conflicts of interest These authors disclose the following: Alex Straumann reports receiving consulting fees from Allakos, AstraZeneca, EsoCap, Dr Falk Pharma, Gossamer, GSK, Receptos-Celgene, and Regeneron-Sanofi; receiving lecture fees from Dr Falk Pharma and Vifor; receiving payment from Dr Falk Pharma for the development of educational presentations; receiving payment from AstraZeneca for serving as member independent data monitor committee; and serving as a board member for European Society of Eosinophilic Oesophagitis (EUREOS) and The International Gastrointestinal Eosinophil Researchers (TIGERS). Alfredo Lucendo reports receiving consulting fees from EsoCap, and Dr Falk Pharma; receiving lecture fees from Dr Falk Pharma; and serving as a board member for EUREOS. Stephan Miehlke reports receiving consulting fees from Celgene, Dr Falk Pharma, and EsoCap; receiving lecture fees from Dr Falk Pharma and Vifor; receiving payment for the development of educational presentations from Dr Falk Pharma; and serving as a board member for EUREOS; Michael Vieth reports receiving lecture fees from Dr Falk Pharma, Janssen-Cilag, Malesci, Menarini, Olympus, and Shire. Christoph Schlag reports receiving consulting fees from Adare, Celgene, EsoCap, and Dr Falk Pharma; receiving lecture fees from Dr Falk Pharma; and serving as a board member for EUREOS. Luc Biedermann reports receiving consulting fees from Calypso Biotech SA, Switzerland; Esocap AG, Switzerland; Vifor AG, Switzerland; receiving lecture fees from Dr Falk Pharma, Germany; Sanofi-Aventis AG, Switzerland; and serving as a board member for EUREOS. Cecilio Santander Vaquero reports receiving lecture fees from Allergan and receiving payment for the development of educational presentations from Laborie. Constanza Ciriza de los Rios reports receiving consulting and/or lecture fees from Allergan and Casen Recordati. Ahmed Madisch reports receiving lecture fees from Dr Falk Pharma. Jamal Hayat reports receiving consulting fees from Dr Falk Pharma; and receiving lecture fees from Dr Falk Pharma. Ulrike von Arnim reports receiving consulting fees from Abbvie, Amgen, Eso Cap, Janssen, MSD, and Takeda; receiving lecture fees from Abbvie, Falk Foundation, Janssen, MSD, Reckitt Benckiser, Takeda, and Vifor; and serving as a board member for EUREOS. Albert Jan Bredenoord reports receiving research funding from Nutricia, Norgine, SideSleepTechnologies, and Bayer; receiving lecture and/or consulting fees from Laborie, Arena, EsoCap, Diversatek, Medtronic, Dr Falk Pharma, Calypso Biotech, Thelial, Robarts, Reckett Benkiser, Regeneron, Celgene, Bayer, Norgine, AstraZeneca, Almirall, Arena, and Allergan. Stefan Schubert reports receiving consulting fees from Abbvie, Takeda, Biogen, Amgen, and Janssen; receiving lecture fees from Abbvie, Dr. Falk Pharma, Takeda, Biogen, Amgen and Janssen; and serving as a board member for MSD, Takeda, and Janssen. Ralph Mueller reports being an employee of Dr Falk Pharma GmbH. Roland Greinwald reports being an employee of Dr Falk Pharma GmbH. Alain Schoepfer reports receiving consulting fees from Abbvie, Adare, Celgene, Dr Falk Pharma, Janssen-Cilag, MSD, Pfizer, Receptos, Regeneron, and Vifor; receiving lecture fees from Abbvie, Celgene, Dr Falk Pharma, Pfizer, Receptos, Regeneron, and Vifor; and serving as a board member for TIGERS. Stephen Attwood reports receiving consulting fees from Dr Falk Pharma, EsoCap, AstraZeneca, and Reckitt Benkiser; receiving lecture fees from Dr Falk Pharma, Medtronic; receiving payment for the development of educational presentations from Dr Falk Pharma. The remaining authors disclose no conflicts.

Funding This study was funded by Dr Falk Pharma GmbH, Freiburg, Germany. Dr Falk Pharma GmbH funded this study and contributed to the design and conduct of the study; collection, management, analysis and scientific interpretation of the data; supported the manuscript preparation and reviewed the manuscript for medical and scientific accuracy. Approval of the manuscript, and the decision to submit the manuscript for publication was the responsibility of the authors.

Author names in bold designate shared co-first authorship.

Authors share co-first authorship.