Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and Rhinoconjunctivitis. |
| Authors: |
Molina-Infante, J Rodriguez-Sanchez, J Martinek, J Van Rhijn, BD Krajciova, J Rivas, MD Barrio, J Moawad, FJ Martinez-Alcala, C Bredenoord, AJ Zamorano, J Dellon, ES
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| Citation: |
Molina-Infante J, etal., Am J Gastroenterol. 2015 Nov;110(11):1567-75. doi: 10.1038/ajg.2015.314. Epub 2015 Sep 29. |
| RGD ID: |
11352743 |
| Pubmed: |
PMID:26416193 (View Abstract at PubMed) |
| DOI: |
DOI:10.1038/ajg.2015.314 (Journal Full-text) |
OBJECTIVES: 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.
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| Genes (Rattus norvegicus) |
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| Cyp2c6 (cytochrome P450, family 2, subfamily C, polypeptide 6) |
| Genes (Mus musculus) |
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| Cyp2c66 (cytochrome P450, family 2, subfamily c, polypeptide 66) |
| Genes (Homo sapiens) |
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| CYP2C19 (cytochrome P450 family 2 subfamily C member 19) |
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