Active Eosinophilic Esophagitis Research Articles

Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial

Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial

Dissociation Between Symptoms and Histological Severity in Pediatric Eosinophilic Esophagitis

The relation between patient symptoms and histological severity of eosinophilic esophagitis (EE) is not known. We created a pediatric EE symptom score (PEESS) and compared the results with histological findings in the esophagus. Subjects ages 3 to 18 years with a histological diagnosis of EE or their parent completed a survey rating the frequency and severity of their gastrointestinal symptoms. Scores ranged from 0 to 98. Eosinophil numbers in esophageal biopsy specimens were correlated with the PEESS. A total of 49 subjects completed the PEESS. The symptom score did not correlate with the peak eosinophil count (r = 0.079). Newly diagnosed, untreated EE subjects (N = 15) had a mean score of 24.7 +/- 16.4 with a modest correlation between the PEESS and the number of eosinophils in the distal esophagus (r = 0.37). The mean PEESS score in the 34 treated patients was lower than in untreated patients (15.6 +/- 12.9; P = 0.046). The mean score for treated patients in histological remission was the same as for treated patients with active EE, regardless of treatment type. Abdominal pain was the most frequent and severe symptom reported. Among 20 of the 34 subjects (58.8%) in histological remission, 17 (85%) continued to report symptoms with a mean score of 17.4 +/- 9.9 (range 1-38). Three children with active histological EE (10%) reported no symptoms. Children with untreated EE had a higher PEESS than treated subjects. Symptoms persisted in 85% of EE patients despite histological resolution and 10% with active EE reported no symptoms. Our data indicate a dissociation between symptoms and histology in pediatric EE.

Budesonide As Induction Treatment For Active Eosinophilic Esophagitis In Adolescents And Adults: A Randomized, Double-blind, Placebo-controlled Study

RATIONALE: Eosinophilic Esophagitis (EoE) is a clinico-pathological defined condition characterized by PPI-refractory esophagus-related symptoms in combination with a dense esophageal eosinophilia. Topical corticosteroids have shown to be effective in children. The purpose of this study is to assess the efficacy of Budesonide in adults with active EoE.

726 Budesonide As Induction Treatment for Active Eosinophilic Esophagitis in Adolescents and Adults: A Randomized, Double-Blind, Placebo-Controlled Study (Bee-I Trial)

726 Budesonide As Induction Treatment for Active Eosinophilic Esophagitis in Adolescents and Adults: A Randomized, Double-Blind, Placebo-Controlled Study (Bee-I Trial)

Mepolizumab, a Humanized Monoclonal Antibody to IL-5, for Severe Eosinophilic Esophagitis in Adults: A Randomized, Placebo-Controlled Double-Blind Trial

This pilot study evaluated the tolerability and efficacy of Mepolizumab (Mepo) in adults with severe Eosinophilic Esophagitis (EE) unresponsive to or dependent on corticosteroids. Eleven adults with active EE (>20 eos/hpf and dysphagia) were randomized to Mepo 750 mg (5, mean age 32 yr) or placebo (Pbo) (6, mean age 34 yr) by intravenous infusion at days 0 and 7. Those not in complete remission at week (Wk) 4 (<5 eos/hpf) received 2 further doses 4 weeks apart, of 1500 mg Mepo or Pbo. From the run-in period (weeks 0 to 4) and throughout the study, subjects received no other anti-eosinophil therapy. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically and via biomarkers of inflammation. No clinically relevant adverse events occurred. A convincing decrease in mean blood eosinophils occurred with Mepo, but not with Pbo. In the esophageal tissue a similar major reduction in mean eosinophil count was observed - 82/hpf at screen to 27 at Wk 4 (-67%) in the Mepo group and from 61 to 45 (-25%) in the Pbo group. The treatment-related changes in eosinophil numbers were associated with much improvement of the swallowing difficulties in 2 subjects at 2 months post last infusion of Mepo, whereas only 1 Pbo-treated subject reported improvement. Treatment of adults with severe EE with Mepo is well tolerated. The blockade of IL-5 resulted in a highly significant decrease of eosinophil numbers in blood and esophageal tissues. These decreases were accompanied by clinical improvement in a subgroup of subjects.

This Month in Gastroenterology

This Month in Gastroenterology

Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Eosinophilic esophagitis in adults – no clinical relevance of wheat and rye sensitizations

Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.

A Randomized, Double-Blind, Placebo-Controlled Trial of Fluticasone Propionate for Pediatric Eosinophilic Esophagitis

Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis. We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 mug of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of </=1 eosinophil in all 400x fields in both the proximal and distal esophagus. Fifty percent of FP-treated patients achieved histologic remission compared with 9% of patients receiving placebo (P = .047). FP decreased esophageal eosinophil levels, with a more pronounced effect in nonallergic individuals (65.9 +/- 25.3 vs 1.4 +/- 1.1 eosinophils/high-power field in the proximal esophagus [P = .03] and 84.6 +/- 19.7 vs 19.6 +/- 12.9 eosinophils/high-power field in the distal esophagus [P = .04]). Resolution of vomiting occurred more frequently with FP than placebo (67% vs 27%; P = .04). FP-induced resolution of mucosal eosinophilia was associated with resolution of endoscopic findings, epithelial hyperplasia, younger age (P = .0003), shorter height (P = .002), and lighter weight (P = .02). Effective treatment with FP decreased the number of CD8(+) T lymphocytes and mast cells in both the proximal and distal esophagus (P < .05). Swallowed FP is effective in inducing histologic remission in eosinophilic esophagitis, with a more pronounced effect in nonallergic and younger individuals, especially in the proximal esophagus.