Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.
Adolescent
Dietary intervention
Eosinophilic esophagitis
Fibrosis
Pediatrics
Proton pump inhibitors
Swallowed topical corticosteroids
Therapeutic use
Journal
European journal of pediatrics
ISSN: 1432-1076
Titre abrégé: Eur J Pediatr
Pays: Germany
ID NLM: 7603873
Informations de publication
Date de publication:
31 May 2024
31 May 2024
Historique:
received:
09
03
2024
accepted:
17
05
2024
revised:
03
05
2024
medline:
31
5
2024
pubmed:
31
5
2024
entrez:
31
5
2024
Statut:
aheadofprint
Résumé
This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.
Identifiants
pubmed: 38819501
doi: 10.1007/s00431-024-05618-z
pii: 10.1007/s00431-024-05618-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Lucendo AJ, Molina-Infante J, Arias A et al (2017) Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United Eur Gastroenterol J 5:335–358. https://doi.org/10.1177/2050640616689525
doi: 10.1177/2050640616689525
Dellon ES, Liacouras CA, Molina-Infante J et al (2018) Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology 155:1022–1033. https://doi.org/10.1053/j.gastro.2018.07.009
doi: 10.1053/j.gastro.2018.07.009
pubmed: 30009819
Feo-Ortega S, Lucendo AJ (2022) Evidence-based treatments for eosinophilic esophagitis: insights for the clinician. Ther Adv Gastroenterol 15:17562848211068664. https://doi.org/10.1177/17562848211068665
doi: 10.1177/17562848211068665
Schoepfer AM, Safroneeva E, Bussmann C et al (2013) Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 145(1230–1236):e1-2. https://doi.org/10.1053/j.gastro.2013.08.015
doi: 10.1053/j.gastro.2013.08.015
Lipka S, Kumar A, Richter JE (2016) Impact of diagnostic delay and other risk factors on eosinophilic esophagitis phenotype and esophageal diameter. J Clin Gastroenterol 50:134–140. https://doi.org/10.1097/MCG.0000000000000297
doi: 10.1097/MCG.0000000000000297
pubmed: 25710524
Dellon ES, Kim HP, Sperry SLW et al (2014) A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease. Gastrointest Endosc 79:577-585.e4. https://doi.org/10.1016/j.gie.2013.10.027
doi: 10.1016/j.gie.2013.10.027
pubmed: 24275329
Laserna-Mendieta EJ, Navarro P, Casabona-Francés S et al (2023) Differences between childhood- and adulthood-onset eosinophilic esophagitis: an analysis from the EoE connect registry. Dig Liver Dis 55:350–359. https://doi.org/10.1016/j.dld.2022.09.020
doi: 10.1016/j.dld.2022.09.020
pubmed: 36280437
Hoofien A, Dias JA, Malamisura M et al (2019) Pediatric eosinophilic esophagitis: results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER). J Pediatr Gastroenterol Nutr 68:552–558. https://doi.org/10.1097/MPG.0000000000002215
doi: 10.1097/MPG.0000000000002215
pubmed: 30540712
Hahn JW, Lee K, Shin JI et al (2023) Global incidence and prevalence of eosinophilic esophagitis, 1976–2022: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 21:3270–3284. https://doi.org/10.1016/j.cgh.2023.06.005
doi: 10.1016/j.cgh.2023.06.005
pubmed: 37331411
Arias Á, Lucendo AJ (2020) Epidemiology and risk factors for eosinophilic esophagitis: lessons for clinicians. Expert Rev Gastroenterol Hepatol 14:1069–1082. https://doi.org/10.1080/17474124.2020.1806054
doi: 10.1080/17474124.2020.1806054
pubmed: 32749898
Robson J, O’Gorman M, McClain A et al (2018) Incidence and prevalence of pediatric eosinophilic esophagitis in Utah based on a 5-year population-based study. Clin Gastroenterol Hepatol 17:107–114. https://doi.org/10.1016/j.cgh.2018.06.028
doi: 10.1016/j.cgh.2018.06.028
pubmed: 29935329
Arias Á, Lucendo AJ (2019) Incidence and prevalence of eosinophilic oesophagitis increase continiously in adults and children in Central Spain: a 12-year population-based study. Dig Liver Dis 51:55–62. https://doi.org/10.1016/j.dld.2018.07.016
doi: 10.1016/j.dld.2018.07.016
pubmed: 30115573
Visaggi P, Savarino E, Sciume G et al (2021) Eosinophilic esophagitis: clinical, endoscopic, histologic and therapeutic differences and similarities between children and adults. Therap Adv Gastroenterol 14:1756284820980860
doi: 10.1177/1756284820980860
pubmed: 33613690
pmcid: 7871287
Hirano I, Chan ES, Rank MA et al (2020) AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology 158:1776–1786. https://doi.org/10.1053/j.gastro.2020.02.038
doi: 10.1053/j.gastro.2020.02.038
pubmed: 32359562
Visaggi P, Barberio B, Del Corso G et al (2023) Comparison of drugs for active eosinophilic oesophagitis: systematic review and network meta-analysis. Gut 72:2019–2030. https://doi.org/10.1136/gutjnl-2023-329873
doi: 10.1136/gutjnl-2023-329873
pubmed: 37491157
Tamarit-Sebastian S, Ferrer-Soler FM, Lucendo AJ (2022) Current options and investigational drugs for the treatment of eosinophilic esophagitis. Expert Opin Investig Drugs 1–18. https://doi.org/10.1080/13543784.2022.2033207
Aceves SS, Alexander JA, Baron TH et al (2022) Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference. Gastrointest Endosc 96:576-592.e1. https://doi.org/10.1016/j.gie.2022.05.013
doi: 10.1016/j.gie.2022.05.013
pubmed: 35965102
Munoz-Persy M, Lucendo AJ (2018) Treatment of eosinophilic esophagitis in the pediatric patient: an evidence-based approach. Eur J Pediatr 177:649–663. https://doi.org/10.1007/s00431-018-3129-7
doi: 10.1007/s00431-018-3129-7
pubmed: 29549437
Laserna-Mendieta EJ, Casabona S, Guagnozzi D et al (2020) Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry. Aliment Pharmacol Ther 52:798–807. https://doi.org/10.1111/apt.15957
doi: 10.1111/apt.15957
pubmed: 32677040
Tourlamain G, Garcia-Puig R, Gutiérrez-Junquera C et al (2020) Differences in management of eosinophilic esophagitis in Europe: an assessment of current practice. J Pediatr Gastroenterol Nutr 71:83–90. https://doi.org/10.1097/MPG.0000000000002672
doi: 10.1097/MPG.0000000000002672
pubmed: 32097371
Chang JW, Saini SD, Mellinger JL et al (2019) Management of eosinophilic esophagitis is often discordant with guidelines and not patient-centered: results of a survey of gastroenterologists. Dis Esophagus Off J Int Soc Dis Esophagus 1(32):doy133. https://doi.org/10.1093/dote/doy133
doi: 10.1093/dote/doy133
Hannan N, Steel A, McMillan SS, Tiralongo E (2020) Health service use and treatment choices for pediatric eosinophilic esophagitis: findings from a cross-sectional survey of Australian carers. Front Pediatr 8:147. https://doi.org/10.3389/fped.2020.00147
doi: 10.3389/fped.2020.00147
pubmed: 32363170
pmcid: 7180181
Zifman E, Banai H, Shamir R et al (2018) Practice differences in the diagnosis and management of eosinophilic esophagitis among adult and pediatric gastroenterologists in Israel. J Pediatr Gastroenterol Nutr 67:34–39. https://doi.org/10.1097/MPG.0000000000001909
doi: 10.1097/MPG.0000000000001909
pubmed: 29394215
Miehlke S, von Arnim U, Schlag C et al (2019) Clinical management of eosinophilic esophagitis — a nationwide survey among gastroenterologists in Germany. Z Gastroenterol 57:745–752. https://doi.org/10.1055/a-0885-1963
doi: 10.1055/a-0885-1963
pubmed: 31170743
Gutiérrez-Junquera C, Fernández-Fernández S, Domínguez-Ortega G et al (2023) Proton pump inhibitor therapy in pediatric eosinophilic esophagitis: predictive factors and long-term step-down efficacy. J Pediatr Gastroenterol Nutr 76(2):191–198. https://doi.org/10.1097/MPG.0000000000003660
doi: 10.1097/MPG.0000000000003660
pubmed: 36416845
Oliva S, Dias JA, Rea F et al (2022) Characterization of eosinophilic esophagitis from the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN. J Pediatr Gastroenterol Nutr 75:325–333. https://doi.org/10.1097/MPG.0000000000003530
doi: 10.1097/MPG.0000000000003530
pubmed: 35706095
Lucendo A, Santander C, Savarino E et al (2022) EoE CONNECT, the European registry of clinical, environmental and genetic determinants in eosinophilic esophagitis: Rationale, design and study protocol of a large-scale epidemiological study in Europe. Ther Adv Gastroenterol
Hirano I, Moy N, Heckman MG et al (2013) Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: Validation of a novel classification and grading system. Gut 62:489–495. https://doi.org/10.1136/gutjnl-2011-301817
doi: 10.1136/gutjnl-2011-301817
pubmed: 22619364
Lucendo AJ, Arias A, Molina-Infante J, Arias-Gonzalez L (2017) The role of endoscopy in eosinophilic esophagitis: from diagnosis to therapy. Expert Rev Gastroenterol Hepatol 11:1135–1149. https://doi.org/10.1080/17474124.2017.1367664
doi: 10.1080/17474124.2017.1367664
pubmed: 28803528
Armstrong D, Marshall JK, Chiba N (2005) Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults — update 2004. Can J Gastroenterol Hepatol 19:15–35. https://doi.org/10.1155/2005/836030
doi: 10.1155/2005/836030
Graham DY, Tansel A (2018) Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 16:800–808.e7. https://doi.org/10.1016/j.cgh.2017.09.033
doi: 10.1016/j.cgh.2017.09.033
pubmed: 28964908
Klok RM, Postma MJ, van Hout BA, Brouwers JRBJ (2003) Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use. Aliment Pharmacol Ther 17:1237–1245. https://doi.org/10.1046/j.1365-2036.2003.01562.x
doi: 10.1046/j.1365-2036.2003.01562.x
pubmed: 12755837
Kirchheiner J, Glatt S, Fuhr U et al (2009) Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol 65:19–31. https://doi.org/10.1007/s00228-008-0576-5
doi: 10.1007/s00228-008-0576-5
pubmed: 18925391
Carrascosa A, Yeste D, Moreno-Galdó A et al (2018) Índice de masa corporal e índice de masa triponderal de 1.453 niños no obesos ni malnutridos de la generación del milenio. Estudio longitudinal de Barcelona An Pediatría 89:137–143. https://doi.org/10.1016/j.anpedi.2017.12.016
doi: 10.1016/j.anpedi.2017.12.016
Carrascosa Lezcano A, Fernández-Cancio M, Yeste D et al. Milennials’ Grouth. Estudio longitudinal de crecimiento. Barcelona 1995–2017
Muftah M, Goldin AH, Barshop K et al (2024) Twice daily PPI induces higher remission rate in eosinophilic esophagitis than once daily regimen regardless of total daily dose. Am J Gastroenterol 119:991–995. https://doi.org/10.14309/ajg.0000000000002712
doi: 10.14309/ajg.0000000000002712
pubmed: 38314789
Laserna-Mendieta EJ, Casabona S, Savarino E et al (2020) Efficacy of therapy for eosinophilic esophagitis in real-world practice. Clin Gastroenterol Hepatol 18:2903-2911.e4. https://doi.org/10.1016/j.cgh.2020.01.024
doi: 10.1016/j.cgh.2020.01.024
pubmed: 31988045
Navarro P, Laserna-Mendieta EJ, Guagnozzi D et al (2021) Proton pump inhibitor therapy reverses endoscopic features of fibrosis in eosinophilic esophagitis. Dig Liver Dis 53:1479–1485. https://doi.org/10.1016/j.dld.2021.05.025
doi: 10.1016/j.dld.2021.05.025
pubmed: 34120859
Casabona-Francés S, Sanz-García A, Ortega GJ et al (2024) A new method to evaluate lower esophageal distension capacity in eosinophilic esophagitis by using functional lumen imaging probe (EndoFLIP™). Diagn Basel Switz 14:218. https://doi.org/10.3390/diagnostics14020218
doi: 10.3390/diagnostics14020218
Gonsalves N, Yang G-Y, Doerfler B et al (2012) Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 142:1451–9.e1; quiz e14–15. https://doi.org/10.1053/j.gastro.2012.03.001
Laserna-Mendieta EJ, Navarro P, Casabona-Francés S et al (2024) Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry. United Eur Gastroenterol J. https://doi.org/10.1002/ueg2.12533
doi: 10.1002/ueg2.12533
Miehlke S, Hruz P, Vieth M et al (2016) A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut 65:390–399. https://doi.org/10.1136/gutjnl-2014-308815
doi: 10.1136/gutjnl-2014-308815
pubmed: 25792708
Ma C, Schoepfer AM, Dellon ES et al (2021) Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS). J Allergy Clin Immunol S0091674921010599. https://doi.org/10.1016/j.jaci.2021.07.001