Effect of Topical Beclomethasone on Inflammatory Markers in Adults with Eosinophilic Esophagitis: A Pilot Study

Abstract

Background:Topical corticosteroids have proven efficacy in the treatment of eosinophilic esophagitis (EoE) and are considered the cornerstone of therapy.Objective:To evaluate the effect of topical beclomethasone dipropionate (BDP) therapy on clinical outcomes, esophageal eosinophilia, and other markers of inflammation in patients with EoE.Methods:Nine subjects with a biopsy-proven diagnosis of EoE were enrolled. In a cross-over design, the subjects were randomly assigned to a sequence of BDP and placebo. Treatment periods were 8 weeks, with a 4-week washout period. The subjects had endoscopic biopsies and blood tests at baseline and after each treatment period. They were instructed to maintain a diary of symptoms. Immuno-histochemical studies were performed for interleukins IL-4, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF) beta. Reverse transcription polymerase chain reaction was performed for IL-3, IL-4, IL-5, IL-10, IL-13, IL-17F, IL-25, IL-33, chemokine ligands (CCL)2, CCL5, CCL11, GM-CSF, and TGF-beta levels. The mast cell tryptase (MCT) level was measured in esophageal tissues.Results:BDP led to a significantly larger decrease in esophageal eosinophilia compared with placebo, but there was no significant change in peripheral eosinophilia and high-sensitivity C-reactive protein between the two groups. The study was not powered enough for us to report a significant improvement in clinical symptoms. There was a significant decrease in tissue IL-13 and MCT levels from baseline to the end of treatment between the treatment and placebo groups. Mean fold decreases in cytokine expression between the baseline and treatment groups were observed for IL-17F, IL-25, CCL2, and CCL5.Conclusion:Treatment with topical BDP was associated with significant decrease in esophageal eosinophilia, MCT and IL-13. BDP is a potential alternative to fluticasone propionate and budesonide for treatment of EoE. Larger studies are needed to validate these findings.

Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters

“…RCTs were excluded if they did not have an explicit glucocorticosteroid vs placebo comparison, 27,[49][50][51] and if they did not include budesonide or fluticasone in the treatment group. 52 Six meta-analyses were reviewed and excluded because they did not include the most recent RCTs published in the field, or included studies in addition to a placebo/glucocorticosteroid comparison. After discussion among the expert panel, the following decisions were made regarding how to pool the data: a single pooled estimate is presented despite differences in type of glucocorticosteroid, delivery mechanism, dosages, patient population (adult/pediatric), and manner of outcome reporting (peak vs mean counts).…”

Orodispersible budesonide tablets for the treatment of eosinophilic esophagitis: a review of the latest evidence

“…Other topical corticosteroids, such as beclomethasone or momethasone, have been studied only in small, mostly uncontrolled, trials. 23–25…”

Heterogeneity in Clinical, Endoscopic, and Histologic Outcome Measures and Placebo Response Rates in Clinical Trials of Eosinophilic Esophagitis: A Systematic Review

“…In contrast, only 13 reported RCTs (59.1%) and four (40%) registered trials defined a priori endoscopic endpoints. Exploratory outcomes were evaluated in 68.2% of reported RCTs (15/22) and included (1) serum or tissue biomarkers (including MIB-1/Ki-67, 19 interleukin [IL] 5, 22,25 IL13, 25,27,35 eotaxin, 22,30 tryptase for mast cells, 19,21,23,25,27,29 tumor necrosis factor, 21,22 tenascin C, 21,27 cytokeratin, 21,23 terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling positive inflammatory and epithelial cells, 21,23 transforming growth factor beta (TGFb), [20][21][22][23]25,27 CD3/8, 19,[21][22][23] eosinophil cationic protein, [21][22][23] eosinophil derived neurotoxin, 22,24 eosinophil peroxidase, 27 serum immunoglobulins, 29 and thymic stromal lymphopoietin 35 ); (2) esophageal thickness 23 (as measured on endoscopic ultrasound); (3) genetic factors associated with EoE (including single nucleotide polymorphisms of TGF-b 20 and measures of the EoE transcriptome 28,30…”

“…Fourteen studies reported change in absolute eosinophil counts before and after therapy or by percentage changes from baseline in eosinophil density. 23,24,[26][27][28][29][30]32,33,35,[37][38][39][40] One study used the EoE Histology Scoring System (EoE-HSS) to evaluate both severity and extent of 8 features (eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis). 38 Four studies specified that histologic outcomes required changes at multiple esophageal levels (eg, proximal and distal esophagus).…”