Efficacy, Dose Reduction, and Resistance to High-Dose Fluticasone in Patients With Eosinophilic Esophagitis

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 147; no. 2; pp. 324 - 333.e5
• Main Authors: Butz, Bridget K, Wen, Ting, Gleich, Gerald J, Furuta, Glenn T, Spergel, Jonathan, King, Eileen, Kramer, Robert E, Collins, Margaret H, Stucke, Emily, Mangeot, Colleen, Jackson, W. Daniel, O'Gorman, Molly, Abonia, J. Pablo, Pentiuk, Scott, Putnam, Philip E, Rothenberg, Marc E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2014
• Subjects: Administration, Oral; Adolescent; Adult; Androstadienes - administration & dosage; Androstadienes - adverse effects; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Dysphagia; Eosinophilic Esophagitis - diagnosis; Eosinophilic Esophagitis - drug therapy; Eosinophilic Esophagitis - genetics; Fluticasone; Gastroenterology and Hepatology; Gene Expression Profiling; Gene Expression Regulation; Humans; Inflammation; Remission Induction; Severity of Illness Index; Steroids; Time Factors; Treatment; Treatment Outcome; United States; Young Adult; United States; PR; Code of Federal Regulations; PPI; FP; partial remission; CFR; EDP; Eosinophilic Esophagitis Diagnostic Panel; Dysphagia; high-power field; BMI; AE; body mass index; adverse event; Inflammation; CR; CCHMC; Treatment; complete remission; Cincinnati Children's Hospital Medical Center; eosinophilic esophagitis; fluticasone propionate; EoE; Steroids; HPF; proton-pump inhibitor
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2014.04.019

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.