Download PDF
Z Gastroenterol 2021; 59(08): 869-878
DOI: 10.1055/a-1429-4192
Übersicht

Therapie der eosinophilen Ösophagitis – Fortschritte und Perspektiven

Treatment of eosinophilic esophagitis – advancements and perspectives
Stephan Miehlke
1   Magen-Darm-Zentrum, Facharztzentrum Eppendorf, Hamburg
2   Speiseröhrenzentrum Universitätsklinikum Hamburg-Eppendorf, Hamburg
,
Ulrike von Arnim
3   Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg
,
Christoph Schlag
4   Medizinische Klinik II, Klinikum Rechts der Isar, Technische Universität, München
,
Joachim Labenz
5   Klinik für Innere Medizin, Diakonie Klinikum Jung-Stilling, Siegen
,
Ahmed Madisch
6   Klinik für Gastroenterologie, KRH Klinikum Siloah, Hannover
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Zusammenfassung

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.

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.

Schlüsselwörter

Eosinophile Ösophagitis - topische Corticosteroide - Budesonid - Fluticason - Protonpumpeninhibitoren - Eliminationsdiät - Biologika

Key words

eosinophilic esophagitis - topical corticosteroids - budesonide - fluticasone - proton pump inhibitor - elimination diet - biological


Publication History

Received: 07 February 2021

Accepted: 07 March 2021

Article published online:
22 June 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Lucendo AJ, Molina-Infante J, Arias Á. et al Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J 2017; 5: 335-358
    CrossrefPubMedGoogle Scholar
  • 2 Navarro P, Arias A, Aria-Gonzalez L. et al Systematic review with meta‐analysis: the growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population‐based studies. Aliment Pharmacol Ther 2019; 49: 1116-1125
    CrossrefPubMedGoogle Scholar
  • 3 Sengupta N, Tapper EB, Corban C. et al The clinical predictors of aetiology and complications among 173 patients presenting to the Emergency Department with oesophageal food bolus impaction from 2004–2014. Aliment Pharmacol Ther 2015; 42: 91-98
    CrossrefPubMedGoogle Scholar
  • 4 Lenz CJ, Leggett C, Katzka DA. et al Food impaction: etiology over 35 years and association with eosinophilic esophagitis. Dis Esophagus 2019; 32: doz010
    PubMedGoogle Scholar
  • 5 Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology 2018; 154: 319-332
    CrossrefPubMedGoogle Scholar
  • 6 Straumann A, Spichtin HP, Grize L. et al Natural History of Primary Eosinophilic Esophagitis: A Follow-up of 30 Adult Patients for Up to 11.5 Years. Gastroenterology 2003; 125: 1660-1669
    CrossrefPubMedGoogle Scholar
  • 7 Schoepfer AM, Safroneeva E, Bussmann C. et al Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 2013; 145: 1230-1236
    CrossrefPubMedGoogle Scholar
  • 8 Warners MJ, Oude Nijhuis RAB, de Wijkerslooth LRH. et al The natural course of eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large cohort. Am J Gastroenterol 2018; 113: 836-844
    CrossrefPubMedGoogle Scholar
  • 9 Shaheen NJ, Mukkada V, Eichinger CS. et al Natural history of eosinophilic esophagitis: a systematic review of epidemiology and disease course. Dis Esophagus 2018; 31 DOI: 10.1093/dote/doy015.
    CrossrefPubMedGoogle Scholar
  • 10 Lucendo AJ, Arias-Gonzalez L, Molina-Infante J. et al Systematic review: health-related quality of life in children and adults with eosinophilic oesophagitis-instruments for measurement and determinant factors. Aliment Pharmacol Ther 2017; 46: 401-409
    CrossrefPubMedGoogle Scholar
  • 11 Alexander R, Alexander JA, Ravi K. et al Measurement of Observed Eating Behaviors in Patients With Active and Inactive Eosinophilic Esophagitis. Clinical Gastroenterology and Hepatology 2019; 17: 2371-2373
    CrossrefPubMedGoogle Scholar
  • 12 Hirano I, Chan ES, Rank MA. et al AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology 2020; 158: 1776-1786
    CrossrefPubMedGoogle Scholar
  • 13 O'Shea KM, Aceves SS, Dellon ES. et al Pathophysiology of Eosinophilic Esophagitis. Gastroenterology 2018; 154: 333-345
    CrossrefPubMedGoogle Scholar
  • 14 Dellon ES, Gupta SK. A Conceptual Approach to Understanding Treatment Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2019; 17: 2149-2160
    CrossrefPubMedGoogle Scholar
  • 15 Miehlke S, Schlag C, Storr M. et al Eosinophilic Esophagitis Update: New Guidelines of the European Study Group EUREOS. Z Gastroenterol 2018; 56: 139-150
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Miehlke S, von Arnim U, Schlag C. et al Clinical Management of Eosinophilic Esophagitis- a nation-wide survey among gastroenterologists in Germany. Z Gastroenterol 2019; 57: 745-752
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Nennstiel S, Schlag C. Treatment of eosinophlic esophagitis with swallowed topical corticosteroids. World J Gastroenterol 2020; 26: 5395-5407
    CrossrefPubMedGoogle Scholar
  • 18 De Heer J, Miehlke S, Rösch T. et al Histologic and Clinical Effects of Different Topical Corticosteroids for Eosinophilic Esophagitis: Lessons from an Updated Meta-Analysis of Placebo-Controlled Randomized Trial. Digestion 2020; 1-9 DOI: 10.1159/000507571.
    CrossrefPubMedGoogle Scholar
  • 19 Gupta SK, Vitanza JM, Collins MH. Efficacy and Safety of Oral Budesonide Suspension in Pediatric Patients With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2015; 13: 66-76
    CrossrefPubMedGoogle Scholar
  • 20 Miehlke S, Hruz P, Vieth M. et al A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut 2016; 65: 390-399
    CrossrefPubMedGoogle Scholar
  • 21 Dellon ES, Katzka DA, Collins MH. et al Budesonide oral suspension improves symptomatic, endoscopic, and histologic parameters compared with placebo in patients with eosinophilic esophagitis. Gastroenterology 2017; 152: 776-786
    CrossrefPubMedGoogle Scholar
  • 22 Lucendo AJ, Miehlke S, Schlag C. et al Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-controlled Trial. Gastroenterology 2019; 157: 74-86
    CrossrefPubMedGoogle Scholar
  • 23 Hirano I, Mukkada VA, Falk GW. et al Efficacy of budesonide oral suspension for eosinophilic esophagitis in adolescents and adults: results from a phase 3 randomized, placebo-controlled tral. Am J Gastroenterol 2019; 114: S205-S206
    CrossrefPubMedGoogle Scholar
  • 24 Hirano I, Safroneeva E, Roumet MC. et al Randomised clinical trial: the safety and tolerability of fluticasone propionate orally disintegrating tablets versus placebo for eosinophilic oesophagitis. Aliment Pharmacol Ther 2020; 51: 750-775
    CrossrefPubMedGoogle Scholar
  • 25 Schlag C, Miehlke S, Lucendo A. et al Efficacy of budesonide orodispersible tablets for induction of remission in patients with active eosinophilic esophagitis: Results from the 6-weeks open-label treatment phase of EOS-2 trial. Gastroenterology 2019; 156: S71
    CrossrefPubMedGoogle Scholar
  • 26 Dellon ES, Katzka DA, Collins MH. et al Safety and Efficacy of Budesonide Oral Suspension Maintenance Therapy in Patients With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2019; 17: 666-673
    CrossrefPubMedGoogle Scholar
  • 27 Straumann A, Lucendo AJ, Miehlke S. et al Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology 2020. S0016-5085(20)35002-2
    PubMedGoogle Scholar
  • 28 Schlag C, Dellon ES, Lucendo AJ. et al Wirksamkeit und Sicherheit der Langzeittherapie der Eosinophilen Ösophagitis mit einer neuen sich im Mund auflösenden Fluticason-Tablette (APT-1011): Ergebnisse einer internationalen randomisierten doppel-blinden Placebo-kontrollierten Phase 2b-Studie. Z Gastroenterol 2020; 58: e129 DOI: 10.1055/s-0040-1716079.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Miehlke S, Lucendo AJ, Straumann A. et al Orodispersible budesonide tablets for the treatment of eosinophilic esophagitis – a review of the latest evidence. Ther Adv Gastroenterol 2020; 13: 1-15
    CrossrefPubMedGoogle Scholar
  • 30 Rokkas T, Niv Y, Malfertheiner P. A Network Meta-Analysis of Randomized Controlled Trials on the Treatment of Eosinophilic Esophagitis in Adults and Children. J Clin Gastroenterol 2020; DOI: 10.1097/MCG.0000000000001356. . Online ahead of print
    CrossrefPubMedGoogle Scholar
  • 31 Lucendo AJ, Arias A, Molina-Infante J. Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients With Symptomatic Esophageal Eosinophilia: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2016; 14: 13-22
    CrossrefPubMedGoogle Scholar
  • 32 Gómez-Torrijos E, García-Rodríguez R, Castro-Jiménez A. et al The efficacy of step-down therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther 2016; 43: 534-540
    CrossrefPubMedGoogle Scholar
  • 33 Laserna-Mendieta EJ, Casabona S, Guagnozzi D. et al Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry. Aliment Pharmacol Ther 2020; 52: 798-807
    CrossrefPubMedGoogle Scholar
  • 34 Miehlke S, von Arnim U, Attwood S. Letter: PPI in EoE: more questions than answers. Aliment Pharmacol Ther 2021; 53: 364-365
    CrossrefPubMedGoogle Scholar
  • 35 Alexander R, Alexander JA, Akambase J. et al Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse. Dig Dis Sci 2020; DOI: 10.1007/s10620-020-06633-4. , epub ahead of print, PMID: 32995996
    CrossrefPubMedGoogle Scholar
  • 36 Vaezi MF, Yang YX, Howden CW. Complications of Proton Pump Inhibitor Therapy. Gastroenterology 2017; 153: 35-48
    CrossrefPubMedGoogle Scholar
  • 37 Daniell HW. Acid suppressing therapy as a risk factor for Candida esophagitis. Dis Esophagus 2016; 29: 479-83
    CrossrefPubMedGoogle Scholar
  • 38 Arias A, Gonzales-Cervera J, Tenias TM. et al Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 2014; 146: 1639-1648
    CrossrefPubMedGoogle Scholar
  • 39 Gonsalves N, Yang GY, Doerfler B. et al Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 2012; 142: 1451-1459
    CrossrefPubMedGoogle Scholar
  • 40 Molina-Infante J, Arias Á, Alcedo J. et al Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study. J Allergy Clin Immunol 2018; 141: 1365-1372
    CrossrefPubMedGoogle Scholar
  • 41 Molina-Infante J, Lucendo AJ. Dietary therapy for eosinophilic esophagitis. J Allergy Clin Immunol 2018; 142: 41-47
    CrossrefPubMedGoogle Scholar
  • 42 Reed CC, Fan C, Koutlas NT. et al Food elimination diets are effective for long-term treatment of adults with eosinophilic oesophagitis. Aliment Pharmacol Ther 2017; 46: 836-844
    CrossrefPubMedGoogle Scholar
  • 43 Schaefer ET, Fitzgerald JF, Molleston JP. et al Comparison of Oral Prednisone and Topical Fluticasone in the Treatment of Eosinophilic Esophagitis: A Randomized Trial in Children. Clin Gastroenterol Hepatol 2008; 6: 165-173
    CrossrefPubMedGoogle Scholar
  • 44 Lucendo AJ, De Rezende LC, Jiménez-Contreras S. et al Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis. Dig Dis Sci 2011; 56: 3551-3558
    CrossrefPubMedGoogle Scholar
  • 45 Straumann A, Hoesli S, Bussmann C. et al Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy 2013; 68: 375-385
    CrossrefPubMedGoogle Scholar
  • 46 Moawad FJ, Molina-Infante J, Lucendo AJ. et al Systematic review with meta-analysis: endoscopic dilation is highly effective and safe in children and adults with eosinophilic oesophagitis. Aliment Pharmacol Ther 2017; 46: 96-105
    CrossrefPubMedGoogle Scholar
  • 47 Dougherty M, Runge TM, Eluri S. et al Esophageal dilation with either bougie or balloon technique as a treatment for eosinophilic esophagitis: a systematic review and meta-analysis. Gastrointest Endosc 2017; 86: 581-591
    CrossrefPubMedGoogle Scholar
  • 48 de Rooij WE, Dellon ES, Parker CE. et al Pharmacotherapies for the Treatment of Eosinophilic Esophagitis: State of the Art Review. Drugs 2019; 79: 1419-1434
    CrossrefPubMedGoogle Scholar
  • 49 Greuter T, Hirano I, Dellon ES. Emerging therapies for eosinophilic esophagitis. J Allergy Clin Immunol 2020; 145: 38-45
    CrossrefPubMedGoogle Scholar
  • 50 Hirano I, Collins MH, Assouline-Dayan Y. et al RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis. Gastroenterology 2019; 156: 592-603
    CrossrefPubMedGoogle Scholar
  • 51 Dellon ES, Collins MH, Rothenberg ME. et al Long-Term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2020; DOI: 10.1016/j.cgh.2020.03.036.
    CrossrefPubMedGoogle Scholar
  • 52 Sastre J, Dávila I. Dupilumab: A New Paradigm for the Treatment of Allergic Diseases. J Investig Allergol Clin Immunol 2018; 28: 139-150
    CrossrefPubMedGoogle Scholar
  • 53 Hirano I, Dellon ES, Hamilton JD. et al Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology 2020; 158: 111-122
    CrossrefPubMedGoogle Scholar
  • 54 Kuang FL, Legrand F, Makiya M. et al Benralizumab for PDGFRA-negative hypereosinophilic syndrome. N Engl J Med 2019; 380: 1336-1346
    CrossrefPubMedGoogle Scholar
  • 55 Greuter T, Straumann A. Medical algorithm: Diagnosis and treatment of eosinophilic esophagitis in adults. Allergy 2020; 75: 727-730
    CrossrefPubMedGoogle Scholar