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Determinants for treatment choice and PPI therapy effectiveness were also assessed. \u00a0A cross-sectional study analysis of patients under 18\u00a0years old recruited onto the multicenter EoE CONNECT registry\u00a0was 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\u2013145) 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\u2009\u00b1\u20090.63 <jats:italic>vs.<\/jats:italic> 0.05\u2009\u00b1\u20090.22, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><jats:p>\u2009\u2009\u2009\u2009<jats:italic>Concl<\/jats:italic><jats:italic>usion<\/jats:italic>: Initial therapy choice for EoE depends on endoscopic phenotype, patient\u2019s age, and patients\u2019 origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.\n<jats:table-wrap><jats:table><jats:tbody>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is Known:<\/jats:bold><jats:italic>\u2022 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.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is New:<\/jats:bold><jats:italic>\u2022 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.<\/jats:italic><jats:italic>\u2022 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.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>","DOI":"10.1007\/s00431-024-05618-z","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:01:53Z","timestamp":1717135313000},"page":"3567-3578","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT 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