title: Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and Rhinoconjunctivitis.
abstract: OBJECTIVE
  Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is diagnosed in at least one-third of patients with suspected eosinophilic esophagitis (EoE). We aimed to evaluate the durability and factors influencing long-term efficacy of PPI therapy.
  
  
  METHODS
  Retrospective multicenter cohort study of patients with PPI-REE who had at least 12 months of follow-up. PPI therapy was tapered to the lowest dose, which maintained clinical remission. Primary outcomes were the proportion of patients with loss of histological response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms were determined from blood samples in a subset of patients.
  
  
  RESULTS
  Seventy-five PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty-five (73%) had sustained histological remission on low-dose PPI therapy. Loss of response was significantly higher in those patients with a CYP2C19 rapid metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs. 13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of loss of response. Among relapsing patients, eosinophilia was limited to the distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia, all showing a CYP2C19 rapid metabolizer genotype, regained histological remission after PPI dose intensification.
  
  
  CONCLUSIONS
  Most PPI-REE patients remain in long-term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and rhinoconjunctivitis were independent predictors of loss of response to PPI, but patients frequently responded to PPI dose escalation.
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Molina-Infante
authors.affiliation: Department of Gastroenterology, Hospital Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Rodriguez-Sanchez
authors.affiliation: Department of Hepato-Gastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Martinek
authors.affiliation: Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Bram D
authors.initials: BD
authors.lastname: van Rhijn
authors.affiliation: Department of Hepato-Gastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Krajciova
authors.affiliation: Research Unit, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Rivas
authors.affiliation: Department of Gastroenterology, Hospital Rio Hortega, Valladolid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Barrio
authors.affiliation: Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Fouad J
authors.initials: FJ
authors.lastname: Moawad
authors.affiliation: Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez-Alcalá
authors.affiliation: Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Bredenoord
authors.affiliation: Research Unit, Hospital San Pedro de Alcantara, Caceres, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Zamorano
authors.affiliation: Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: Evan S
authors.initials: ES
authors.lastname: Dellon
mesh_terms: D000293:Adolescent; D000328:Adult; D003231:Conjunctivitis / Q000150:complications; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004361:Drug Tolerance; D004802:Eosinophilia / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004935:Esophageal Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012220:Rhinitis / Q000150:complications; D013997:Time Factors; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19