Aerosolized Fluticasone for EoE Improved Histology but Not Dysphagia

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.