Fluticasone Shows Histologic Improvement, But No Improvement in Symptoms in Eosinophilic Esophagitis

Nancy A. Melville

October 22, 2010

October 22, 2010 (San Antonio, Texas) — In the first controlled trial of swallowed fluticasone spray for the treatment of eosinophilic esophagitis, the corticosteroid therapy was shown to offer substantial histologic improvement of the condition. However, the improvement did not translate into a significant difference in the resolution of symptoms between the treatment and placebo groups, according to research presented here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.

For the trial, 42 patients were randomized to receive twice-daily aerosolized swallowed fluticasone 880 μg over 6 weeks or placebo; 34 patients completed the trial.

A significant histologic response was seen in 71% of the fluticasone group, compared with 10% of the placebo group (P < .01). Symptom response, however, was similar between the 2 groups: in an intention-to-treat analysis, symptom response was 71% with fluticasone and 48% with placebo; in a per protocol analysis, it was 68% and 74%, respectively, reported lead investigator Jeffrey A. Alexander, MD, from the Mayo Clinic in Rochester, Minnesota.

The study involved patients who had a peak number of 15 or more eosinophils per high-power field on esophageal biopsies, and who had persistent dysphasia after 4 weeks of twice-daily proton-pump inhibitor therapy. Age, sex, endoscopic findings, and allergic history were similar between the 2 groups.

Dysphagia symptoms were assessed at baseline and at 2, 4, and 6 weeks, using the Mayo Dysphagia Questionnaire-2 Week, an assessment of symptomatic response, histologic response, and endoscopic features, including rings, furrow, white spots, and nondistal structure.

Urine cortisol, endoscopy, and biopsy results were monitored 6 weeks after the initiation of treatment.

As with symptom response, the frequency of abnormal endoscopic findings was similar between the 2 groups: for fluticasone, the frequency was 79% before treatment and 68% after 6 weeks of treatment; for placebo, the frequency was 80% and 88%, respectively.

Posttreatment 24-hour urine cortisol levels were also similar (23.2 ± 2.3 μg for fluticasone vs 15.5 ± 2.5 μg for placebo).

A steroid applied to the esophagus is often used to treat eosinophilic esophagitis. Dr. Alexander said his clinical impression has been that the therapy does improve symptoms; however, there is no scientific proof of its effectiveness.

The gap observed between histologic and symptom improvement in the study might be the result of several factors, including the fact that lesions in some patients do not respond well or as quickly to steroids, and the simple need for a more accurate assessment tool, Dr. Alexander told Medscape Medical News.

"Eosinophilic esophagitis can cause scarring in the wall of the esophagus in some patients, causing the esophagus to become narrowed and difficult to distend," he explained. "In those patients, response to steroids is probably is less impressive."

"We didn't see that with the scope, but you can still have some subtle changes that aren't picked up with the scope," Dr. Alexander observed.

"Furthermore, the instrument we used to assess the patients' symptoms — a validated dysphasia questionnaire — wasn't entirely accurate at truly assessing symptoms. It's very difficult to ask these people if, for example, they had food stick in their esophagus over the past 2 weeks and to get a true idea of how their swallowing is going."

"The fact that the eosinophils go away is very important, however. It means we're turning off the process, and that's what we aim to do," he said.

Despite the lack of a significant difference in symptom response, Naim Alkhouri, MD, a gastroenterology fellow at The Cleveland Clinic in Ohio, agreed that the findings are important.

"This was an interesting paper. I certainly wouldn't say it was a negative study, because the histologic response really was quite impressive," he said. "In the long term, people with eosinophilic esophagitis could benefit from being on fluticasone, but this is a relatively new disease, so there is still much about it that we need to better understand."

The study received funding from the Fitterman Grant to the Mayo Division of Gastroenterology. Dr. Alexander reports being a consultant for Meritage Pharma and receiving funding for research from Merck. Dr. Alkhouri has disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 1. Presented October 18, 2010.

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