Stephan Miehlke

Background: Eosinophilic esophagitis (EoE) is a chronic, progressive, immune-mediated disease of the esophagus. Esophageal dysfunction in solid food dysphagia combined with eosinophil-dominant inflammation (⩾15 eos/high-power-field (hpf)) serves as diagnostic criteria. Treatment objectives for active EoE include induction and maintenance of clinical-histological remission. Topical budesonide therapy in the form of an orodispersible tablet (BUD-ODT) has shown effectiveness in both scenarios. Objectives: To examine the efficacy and safety of BUD-ODT therapy in adults with active EoE in a Real-World-Setting. Design: This retrospective study from two German EoE centers examined the efficacy and safety of BUD-ODT therapy in adults with active EoE between June 2018 and August 2022. Methods: Patient demographics, clinical characteristics, and EoE history were extracted from medical records. Evaluations included clinical (Straumann Dysphagia Index, range: 0–9, remission: ⩽3 points), histological (remission: ⩽15 eos/hpf), and endoscopic assessment (endoscopic reference scoring system (EREFS) score, range: 0–9, remission: ⩽2 points). Three periods were analyzed: Induction phase (induction therapy (IT): 1 mg BID, 6–12 weeks; n = 201), maintenance phase I (RM1: 0.5 mg BID or 1 mg QD, 14–24 weeks; n = 109), and maintenance phase II (RM2: same dosage as RM1, 52–104 weeks; n = 72). Results: A total of 221 adults with clinical-histologically proven active EoE were included. Clinical-histological remission was achieved in 75.1% (151/201) of patients after IT, maintained in 73.4% (80/109) after RM1, and in 76.4% (55/72) after RM2. The relapse rate was 26.6% (29/109) after RM1 and 23.6% (17/72) after RM2. Those patients underwent re-induction therapy for 6–8 weeks and were re-evaluated separately (remission: 36.0% after RM1 and 46.2% after RM2). Endoscopic remission was demonstrated in 88.1% (177/201) after IT. The most prevalent side effect was endoscopically detected combined oral-esophageal candidiasis. Conclusion: BUD-ODT demonstrated high effectiveness in inducing and maintaining remission in a real-world setting. The spectrum of side effects did not reveal any new aspects compared to known clinical data.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline “Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus—version 3.1” is to provide practical and evidence‐based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well‐established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage‐appropriate therapy after the initial diagnosis of esophageal cancer. In high‐grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD‐L1 and/or Her2 expression.

In jüngster Zeit wurden in der Therapie der eosinophilen Ösophagitis (EoE) und insbesondere im Bereich der topischen Corticosteroide erhebliche Fortschritte erreicht. Neue EoE-spezifische Darreichungsformen wurden entwickelt und haben in Form der orodispersiblen Budesonid-Tablette zu der ersten in Deutschland und anderen europäischen und außereuropäischen Ländern zugelassenen Therapie der EoE bei Erwachsenen geführt. In den USA steht eine EoE-spezifische orale Budesonid-Suspension kurz vor der Zulassung. Dagegen bleibt die wissenschaftliche Datenlage zur Wirksamkeit von Protonenpumpeninhibtoren weiterhin limitiert. Auch im Bereich der Biologika konnten nach langer Zeit Substanzen identifiziert werden, die erstmals in Phase 2 sehr vielversprechende Ergebnisse gezeigt haben und sich derzeit in klinischen Prüfungen der Phase 3 befinden. In diesem Artikel sollen die aktuellen Fortschritte und Perspektiven in der Therapie der EoE dargestellt und diskutiert werden. In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE. Received: 07 February 2021 Accepted: 07 March 2021 Article published online: 04 May 2023 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Die eosinophile Ösophagitis (EoE) ist eine immunvermittelte, chronische Erkrankung der Speiseröhre, die durch ösophageale Symptome und histologisch durch eine eosinophile-prädominante Inflammation gekennzeichnet ist. Unbehandelt führt die EoE langfristig zu ösophagealer Fibrose und Strikturen sowie in seltenen Fällen zu schwerwiegenden Komplikationen. Das Therapieziel besteht in der Induktion und der langfristigen Erhaltung einer klinisch-histologischen Remission. Article published online: 11 October 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background: A novel budesonide orodispersible tablet (BOT) has been proven effective in adult patients with active eosinophilic oesophagitis (EoE) in a 6‐week placebo‐controlled trial (EOS‐1).Aims: To report the efficacy of an open‐label induction treatment with BOT in a large prospective cohort of EoE patients within the EOS‐2 study.Methods: Patients with clinico‐histological active EoE were treated with BOT 1 mg BID for 6 weeks. The primary endpoint was clinico‐histological remission (≤2 points on numerical rating scales [0–10] each for dysphagia and odynophagia, and peak eosinophil count 2 hpf (corresponds to 2 hpf (i.e., by 89.0%). Mean EEsAI‐PRO score decreased from baseline by 29 points and deep endoscopic remission was achieved in 97 (53.6%) patients. The majority of patients judged tolerability as good or very good (85.6%) and compliance was high (96.5%). Local candidiasis was suspected in 8.3% of patients; all were of mild severity, resolved with treatment and none led to premature withdrawal from the study.Conclusions: In this large prospective trial, a 6‐week open‐label treatment with BOT 1 mg BID was highly effective and safe in achieving clinico‐histological remission of active EoE and confirmed the results of the placebo‐controlled EOS‐1 trial.

Zusammenfassung In jungster Zeit wurden in der Therapie der eosinophilen osophagitis (EoE) und insbesondere im Bereich der topischen Corticosteroide erhebliche Fortschritte erreicht. Neue EoE-spezifische Darreichungsformen wurden entwickelt und haben in Form der orodispersiblen Budesonid-Tablette zu der ersten in Deutschland und anderen europaischen und au ss ereuropaischen Landern zugelassenen Therapie der EoE bei Erwachsenen gefuhrt. In den USA steht eine EoE-spezifische orale Budesonid-Suspension kurz vor der Zulassung. Dagegen bleibt die wissenschaftliche Datenlage zur Wirksamkeit von Protonenpumpeninhibtoren weiterhin limitiert. Auch im Bereich der Biologika konnten nach langer Zeit Substanzen identifiziert werden, die erstmals in Phase 2 sehr vielversprechende Ergebnisse gezeigt haben und sich derzeit in klinischen Prufungen der Phase 3 befinden. In diesem Artikel sollen die aktuellen Fortschritte und Perspektiven in der Therapie der EoE dargestellt und diskutiert werden. Abstract In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S.In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.