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Predicting resistance to high-dose fluticasone in eosinophilic esophagitis

A study in August's issue of Gastroenterology evaluates the efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis.

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Dr Marc Rothenberg and colleagues from Ohio, USA evaluated the efficacy and safety of high-dose swallowed fluticasone propionate, and dose reduction in patients with eosinophilic esophagitis.

The research team analyzed esophageal transcriptomes to identify mechanisms.

The researchers conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg fluticasone propionate in participants age 330 years with active eosinophilic esophagitis.

The team reported that 28 participants received fluticasone propionate, and 14 participants received placebo.

After 3 months, participants given fluticasone propionate who were in complete remission received 880 mcg fluticasone propionate daily.

65% of subjects given fluticasone propionate were in complete remission after 3 months
Gastroenterology

Participants in the fluticasone propionate or placebo groups who were not in complete remission continued or started, respectively, 1760 mcg fluticasone propionate daily for 3 additional months.

The team's primary end point was histologic evidence for complete remission.

Secondary end points were partial remission, symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and fluticason propionate responsiveness.

After 3 months, the team found that 65% of subjects given fluticasone propionate and no subjects given placebo were in complete remission.

The research team observed that 12% of those given fluticasone propionate, and 8% of those given placebo were in partial remission.

In the fluticasone propionate group, 73% of subjects remained in complete remission, and 20% were in partial remission after the daily dose was reduced by 50%.

Extending fluticasone propionate therapy in fluticasone propionate-resistant participants did not induce remission.

The researchers observed that fluticasone propionate decreased heartburn severity.

Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to fluticasone propionate.

Gene expression patterns in esophageal tissues of fluticasone propionate responders were similar to those of patients without EoE.

The researchers found evidence for heterogeneous steroid signaling in subjects who did not respond to fluticasone propionate, and preliminary evidence for transcripts predictive of fluticasone propionate responsiveness.

Dr Rothenberg's team commented, "Daily administration of a high dose of fluticasone propionate induces histologic remission in 65%77% of patients with eosinophilic esophagitis after 3 months."

"A 50% dose reduction remained effective in 73%93% of patients who initially responded to fluticasone propionate."

"Nonresponders had evidence of steroid resistance."

"Histologic and molecular markers may predict resistance."

Gastroenterol 2014: 147(2): 324333.e5
29 July 2014

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