Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy

Abstract

Objectives: To assess the short-and long-term efficacy of proton pump inhibitor (PPI) therapy for pediatric eosinophilic esophagitis (EoE) in realworld practice with a step-down strategy, and to evaluate factors predictive of PPI responsiveness. Methods: We collected data regarding the efficacy of PPIs during this crosssectional analysis of the prospective nationwide RENESE registry. Children with EoE treated with PPI monotherapy were included. Histological remission was defined as a peak eosinophilic count of <15 eosinophils (eos)/ high-power field (hpf). Factors associated with PPI responsiveness were identified using multivariate logistic regression analysis. Results: After induction therapy, histological and clinico-histological remission were observed in 51.4% (n = 346) and 46.5% of children, respectively. Normal endoscopic appearance of the esophagus was associated with a higher possibility [odds ratio (OR), 9.20; 95% confidence interval (CI), 2.10-40.16], and fibrostenotic phenotype was associated with a lower possibility (OR, 0.36; 95% CI, 0.18-0.74) of histological remission. Long-term therapy with a step-down strategy effectively maintained histological remission in 68.5% and 85.3% of children at 7 months (n = 108) and 16 months (n = 34), respectively. Complete initial histological remission (≤5 eos/hpf) was associated with a higher possibility of sustained histological remission (OR, 5.08; 95% CI, 1.75-14.68). Adverse events were infrequent and mild. Conclusions: We confirmed the efficacy of PPIs for a large cohort of children with EoE with sustained histological remission using a stepdown strategy. Children with fibrostenotic phenotypes are less likely to respond to induction therapy. Furthermore, patients with complete initial histological remission are more likely to experience long-term histological remission.

Proton pump Inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction and evaluation of treatment response

“…Around 70-80% of those EoE patients in whom high PPI doses achieve histological and clinical remission maintain long-term remission after a dose reduction 29,30 . Our results demonstrate that short-term PPI treatment restores the accumulation of proteins related to inflammation and epithelial differentiation processes such as cornification (Figure 4) , suggesting that it might also prevent long-term complications of EoE such as scarring and narrowing of the esophagus 28 .…”

Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics

“…The abovementioned meta-analysis included 188 children, among whom PPI therapy resulted in a summary estimate effectiveness of 54% [ 48 ]. More recently, an analysis of the prospective Spanish nationwide RENESE registry found that histological and clinico-histological remission was observed in 51.4% and 46.5% of the 346 children included [ 52 ].…”

“…For pediatric patients, 70–78% of initial responders to double doses remained in clinical and histological remission on tapering maintenance doses of 1 mg/kg/day after one year [ 51 , 55 ]. These figures were reproduced by large registries of clinical practice [ 24 , 52 ].…”

“…The initial response to PPI therapy has been associated with some clinical and endoscopic aspects. Neither the age nor the sex of the patient determines the effectiveness of this therapy, nor does its use as the first or as a subsequent line of treatment (after failure of dietary therapy or swallowed topical corticosteroids) [ 52 , 59 , 60 ]. On the other hand, an increased body mass index was found to reduce the chances of achieving remission with PPIs [ 61 ].…”

“…On the other hand, an increased body mass index was found to reduce the chances of achieving remission with PPIs [ 61 ]. The presence of fibro-stricturing endoscopic features (esophageal rings or strictures) has consistently been shown to reduce the chances of response to PPI [ 24 , 52 , 59 , 62 ], which could explain why patients who debuted with food impaction also had a higher probability of PPI therapy failure (adjusted odds ratio = 2.8, 95% confidence interval [CI]: 1.1–7.4) [ 63 ]. Edema and vertical lines are other endoscopic features that are found more commonly in children who did not respond to PPIs [ 64 ].…”