Oral Viscous Steroid Beats Nebulizer in EoE

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02) (Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049]).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

"In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02) (Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049]).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

"In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02) (Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049]).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

"In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.