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

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 3–30 years old with active EoE. Twenty-eight participants received FP and 14 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 endpoint was histologic evidence for CR. Secondary endpoints 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 that did not respond to FP. 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 that initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283

Systematic review of histological remission criteria in eosinophilic esophagitis

“…Although there were no common criteria to define histological remission in the studies reviewed, a majority of the randomized controlled trial studies used more stringent values ranging from 0 to ≤5 eosinophils/hpf to define histological remission or resolution 22, 26, 66, 67, 68. Compared to dietary treatment studies (e.g.…”

Eosinophilic Esophagitis–More than Two Decades of Progress

“…Histologic response was seen in the topical steroid group, however dysphagia was not significantly reduced in the treatment group (63% fluticasone group and 47% placebo group; (P = 0.49) [57]. In a study by Butz et al in 2014, recommended that patients being treated with high dose fluticasone (1760 mcg) should be followed up in 3 months for response and can either have dose reduction to 880 mcg or continue with high dose for another 3 months [58]. Due to the difficulty aerosolized corticosteroids may be for young children to ingest, Aceves et al used viscous budesonide to treat pediatric patients with EoE with significant reduction in symptoms and histology [59,60].…”

Infective Esophagitis: Inhaled Steroids Treatment for Eosinophilic Esophagitis not Always Safe

“…A recent randomized trial evaluated the efficacy and safety of high-dose swallowed fluticasone and dose reduction in patients with EoE. At least 3 months of Fluticasone induced histologic remission in 65%-77% of patients and 50% dose reduction remained effective in 73%-93% of patients who initially responded to it [15]. This suggests that all the patients should have dose reduction following a repeat endoscopy documenting histological response at the end of 3 months and then continued on lowest effective dose with appropriate follow up.…”