s-1743 and Eosinophilic-Esophagitis

In order to provide a comparative evaluation of available pharmacologic treatments for eosinophilic esophagitis (EoE), we conducted a network meta-analysis.. A variety of pharmacologic treatments for EoE have been reported, however there exists a paucity of direct comparisons.. We searched randomized controlled trials using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials database through December 2014. Studies were analyzed using a random-effects network meta-analysis to identify the most effective therapy. Subgroup analysis was performed among studies that excluded gastroesophageal reflux disease or proton-pump inhibitor responsive esophageal eosinophilia, and also among pediatric and adult populations. The ranking probability for the efficacy of each treatment was analyzed. Consistency of the included randomized controlled trials was checked by applying inconsistency and node-splitting models.. Eleven studies of a total of 456 patients were identified. Six pharmacologic treatments (budesonide suspension and viscous, fluticasone, prednisone, esomeprazole, and mepolizumab) and placebo were included in our analysis. Meta-analysis showed superiority of budesonide viscous, budesonide suspension, and fluticasone over placebo. Network meta-analysis demonstrated the rank order of efficacy as budesonide viscous, esomeprazole, prednisone, budesonide suspension, fluticasone, mepolizumab, and placebo. The results were consistent from the inconsistency model analysis and node-splitting analysis. Subgroup analysis demonstrated prednisone, budesonide suspension, and esomeprazole were the most effective when network meta-analyses were performed among studies that excluded gastroesophageal reflux disease or proton-pump inhibitor responsive esophageal eosinophilia, and among pediatric and adult populations, respectively.. On the basis of this network meta-analysis, viscous budesonide was shown to be the most effective pharmacologic therapy for EoE among the reported pharmacologic treatments.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Budesonide; Child; Child, Preschool; Eosinophilic Esophagitis; Esomeprazole; Female; Fluticasone; Gastrointestinal Agents; Glucocorticoids; Humans; Infant; Male; Middle Aged; Prednisone; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Young Adult

Proton-pump inhibitor-responsive esophageal eosinophilia is a newly recognized entity with an unclear prevalence in children, as only retrospective data are available. The aim of this study was to determine the prevalence and clinical features of proton-pump inhibitor-responsive esophageal eosinophilia in children.. This prospective study enrolled patients with esophageal symptoms and esophageal eosinophilic counts as 15 or more than 15 eos/hpf (eosinophils per high-power field). Children received treatment with esomeprazole 1 mg · kg per dose twice daily for 8 weeks and the endoscopy was repeated. Complete response to proton-pump inhibitor (PPI) was defined as 5 or less than 5 eos/hpf, and a partial response as >5 and <15 eos/hpf in post-treatment biopsies.. Fifty-one children (74.5% boys) were included. Histological response was observed in 35 children (68.6%): 24 children (47%) had a complete response and 11 children (21.6%) had a partial response. Only 16 children (31.4%) were diagnosed with eosinophilic esophagitis (EoE). There were no differences in history of atopy, allergy tests, pH study results, and endoscopic scores. Clinical symptoms were similar, with the exception of food impaction, which was more frequent in children with EoE (56.2% vs 20%, P = 0.01). The mean pretreatment peak eosinophil count was higher in patients with EoE (74.8 ± 36.2 vs 46.3 ± 30.7, P = 0.007). Eleven of the 14 patients (78.6%) on a lower PPI treatment maintenance dose remained in clinicopathologic remission at 1-year follow-up.. A significant proportion of children with esophageal eosinophilia responded to high dose PPI treatment. Clinical, endoscopic, and pH study results were similar, with exception of patients with EoE, who were more likely to experience food impaction and have higher esophageal eosinophil counts.

Topics: Adolescent; Child; Child, Preschool; Deglutition Disorders; Drug Administration Schedule; Eosinophilic Esophagitis; Esomeprazole; Esophagoscopy; Female; Humans; Infant; Male; Prevalence; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome

Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE).. To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm.. Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group).. Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission.. Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Combined Modality Therapy; Eosinophilic Esophagitis; Esomeprazole; Female; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Recurrence; Remission Induction; Treatment Outcome

Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole.. This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as <7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment.. Forty-two patients (90% male, 81% white, mean age 38 ± 10 years) were randomized into fluticasone (n = 21) and esomeprazole (n = 21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n = 4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P = 0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P = 0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P = 1.00). The MDQ score significantly decreased after treatment with esomeprazole (19 ± 21 vs. 1.4 ± 4.5, P<0.001), but not with fluticasone (17 ± 18 vs. 12 ± 16, P = 0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups.. Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Anti-Ulcer Agents; Eosinophilic Esophagitis; Esomeprazole; Female; Fluticasone; Humans; Male; Middle Aged; Single-Blind Method; Treatment Outcome

The consensus statements for eosinophilic oesophagitis recommend that ambulatory pH monitoring is one means of determining if gastro-oesophageal reflux is the cause of oesophageal eosinophilia and should guide pharmacological therapy.. To evaluate prospectively the accuracy of pH monitoring as a predictor of endoscopic, histological and symptomatic response in patients with oesophageal eosinophilia.. We conducted a prospective trial in which patients with oesophageal eosinophilic infiltration with ≥15 eos/hpf underwent a 24-h pH study and were placed in one of two treatment arms for 6 weeks based on positive or negative results. Patients with abnormal acid exposure were treated with esomeprazole 40 mg twice daily and others were treated with oral viscous budesonide 1 g twice daily. Response to treatment was assessed by oesophageal histology (<5 eos/hpf) and symptoms.. A total of 51 patients were enrolled in the study. The average patient age was 39 years and 31 patients (61%) were male. The average number of eosinophils per hpf, prior to study enrolment was 41.2 (range 15-140, s.d. 27.7). Nineteen (37%) had positive pH studies and 32 (63%) had negative pH studies. Eighteen patients completed treatment with esomeprazole. Only eleven (61%) had histological response and, of these eleven, five (46%) had symptomatic improvement. A total of 28 patients with normal acid exposure completed treatment with budesonide. Only 16 (57%) had histological and 11 (69%) had symptomatic improvement.. In this prospective trial of pH-guided treatment, neither positive nor negative results of initial pH monitoring accurately predicted response to therapy.

Topics: Adult; Aged; Anti-Inflammatory Agents; Anti-Ulcer Agents; Budesonide; Eosinophilic Esophagitis; Esomeprazole; Female; Gastric Acidity Determination; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Monitoring, Ambulatory; Predictive Value of Tests; Prospective Studies; Severity of Illness Index; Treatment Outcome

Proton pump inhibitor (PPI)-responsive eosinophilic esophagitis (EoE) is frequently observed in children, but data on long-term treatment are scarce. The objective of this study is to evaluate the long-term efficacy and safety of PPIs in children with EoE.. This prospective study enrolled children with EoE and histological remission to an 8-week esomeprazole trial (1 mg/kg/dose, twice daily). Esomeprazole was maintained at 1 mg/kg/day for 1 year. Symptom recurrence and adverse events were monitored and a follow-up endoscopy was performed at 12 months. Complete histological remission was defined as ≤5 eosinophils/high-power field (eos/hpf), and partial histological remission as >5 and <15 eos/hpf. Patients had no concomitant dietary restrictions or topical steroid.. Fifty-seven children were included. Histological remission on maintenance PPI therapy was present in 40 children (70.1%; 95% CI 56.5-81.5). Long-term remission rate was higher in children with initial complete histological remission than in those with partial remission (81% vs 50%, P = 0.014). Forty-nine children (86%) remained asymptomatic. Pretreatment clinical and histological findings and median PPI dose/kg/day were similar between relapsers and nonrelapsers. Eleven out of 12 children (91.6%) receiving esomeprazole 0.5 mg · kg ·  day for 12 additional months remained in remission. Mild and transient side effects without requiring PPI avoidance were observed in 5 children.. Up to 70% of children with PPI-responsive EoE remain in histological and clinical remission on a low-dose maintenance treatment at 1-year follow-up, with adequate safety profile. Complete histological remission to an 8-week PPI trial was associated with higher probability of histological remission on maintenance therapy.

Topics: Administration, Oral; Adolescent; Child; Child Health Services; Child, Preschool; Drug Administration Schedule; Eosinophilic Esophagitis; Esomeprazole; Esophagoscopy; Female; Humans; Infant; Male; Prospective Studies; Proton Pump Inhibitors; Recurrence; Remission Induction; Spain; Treatment Outcome

Topics: Aged; Anti-Inflammatory Agents; Anti-Ulcer Agents; Back Pain; Diagnosis, Differential; Eosinophilic Esophagitis; Esomeprazole; Esophagoscopy; Esophagus; Humans; Male; Prednisolone; Proton Pump Inhibitors; Recurrence; Treatment Failure; Treatment Outcome

Interaction with gastroesophageal reflux disease (GERD) has been a fundamental consideration in eosinophilic esophagitis (EoE) since the initial reports of this emerging entity. While studies from the '80s identified the presence of esophageal eosinophilia as being a histologic marker for the diagnosis of GERD, studies in the '90s demonstrated that high levels of esophageal eosinophilia were characteristic for a novel immune/antigen-mediated esophageal disease, EoE, that was seemingly quite distinct from GERD. However, several recent studies have demonstrated the effectiveness of proton pump inhibition (PPI) in reducing symptoms and histopathology in a subset of patients with esophageal eosinophilia and suspected EoE, leading to the terminology "PPI responsive esophageal eosinophilia." It remains uncertain as to whether these patients have EoE, GERD, or a PPI responsive esophageal inflammatory condition that is distinct from either GERD or EoE. Emerging translational research has evidenced mechanisms by which PPI response in patients with esophageal eosinophilia may be a consequence of PPI effects on the immune pathogenesis of EoE. Therefore, a symptom and histologic response to PPI in patients with esophageal eosinophilia does not necessarily "rule in" GERD. Until further studies better define the pathogenesis of PPI responsive esophageal eosinophilia, a trial of PPI therapy remains an important prerequisite to the diagnosis EoE. Following this diagnostic approach allows for the clinical application of available evidence that is derived from research trials in EoE that exclude PPI responsive eosinophilia.

Topics: Androstadienes; Anti-Inflammatory Agents; Anti-Ulcer Agents; Eosinophilic Esophagitis; Esomeprazole; Female; Fluticasone; Humans; Male