Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis.
OBJECTIVE
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.
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Bridget K
BK
Butz
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Ting
T
Wen
Department of Dermatology, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, Utah.
Gerald J
GJ
Gleich
Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
Glenn T
GT
Furuta
Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Jonathan
J
Spergel
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Eileen
E
King
Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
Robert E
RE
Kramer
Division of Pathology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Margaret H
MH
Collins
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Emily
E
Stucke
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Colleen
C
Mangeot
Division of Pediatric Gastroenterology, University of Utah, Salt Lake City, Utah.
W Daniel
WD
Jackson
Division of Pediatric Gastroenterology, University of Utah, Salt Lake City, Utah.
Molly
M
O'Gorman
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
J Pablo
JP
Abonia
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Scott
S
Pentiuk
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Philip E
PE
Putnam
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. Electronic address: rothenberg@cchmc.org.
Marc E
ME
Rothenberg
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D057765:Eosinophilic Esophagitis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000068298:Fluticasone; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000068298:Fluticasone
Dysphagia; Inflammation; Steroids; Treatment