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Gastroenterology. 2014 Aug;147(2):324-33.e5. doi: 10.1053/j.gastro.2014.04.019. Epub 2014 Apr 22.

Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis.

Author information

1
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
2
Department of Dermatology, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, Utah.
3
Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
4
Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
5
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
6
Division of Pathology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
7
Division of Pediatric Gastroenterology, University of Utah, Salt Lake City, Utah.
8
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
9
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. Electronic address: rothenberg@cchmc.org.

Abstract

BACKGROUND & AIMS:

We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms.

METHODS:

We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness.

RESULTS:

After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness.

CONCLUSIONS:

Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.

KEYWORDS:

Dysphagia; Inflammation; Steroids; Treatment

PMID:
24768678
PMCID:
PMC4107112
DOI:
10.1053/j.gastro.2014.04.019
[Indexed for MEDLINE]
Free PMC Article

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