Dietary Elimination Therapy Is Effective in Most Adults With Eosinophilic Esophagitis Responsive to Proton Pump Inhibitors.
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ABSTRACT:
SUBMITTER: Iglesia EGA
PROVIDER: S-EPMC7008080 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundProton pump inhibitors (PPIs) are a first-line treatment for EoE, but data are limited concerning response durability. We aimed to determine long-term outcomes in EoE patients responsive to PPI-therapy.MethodsWe conducted a retrospective cohort study of newly diagnosed adults with EoE who had initial histologic response (<15 eosinophils per high-power-field) to PPI-only therapy. We extracted data regarding their subsequent clinical course and outcomes. We compared findings between the initial PPI-response endoscopy and the final endoscopy, and assessed factors associated with loss of PPI response.ResultsOf 138 EoE patients with initial histologic response to PPI, 50 had long-term endoscopic follow-up, 40 had clinical follow-up, 10 changed treatments, and 38 had no long-term follow-up. Of those with endoscopic follow-up, mean follow-up-time was 3.6 ± 2.9 years; 30 and 32 patients (60%; 64%) maintained histologic and symptom responses, respectively. However, fibrotic endoscopic findings of EoE were unchanged. Younger age (aOR 1.05, 95% CI: 1.01-1.11) and dilation prior to PPI treatment (aOR 0.21, 95% CI: 0.05-0.83) were the only factors associated with long-term loss of PPI response.ConclusionsLong-term histologic and clinical response rates for PPI therapy were 60% and 64%, respectively. Younger age and dilation at baseline were associated with histologic loss of response. These data can inform long-term EoE treatment selection.
| S-EPMC9427674 | biostudies-literature
Project description:Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US$ 1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation.
| S-EPMC4644096 | biostudies-other
Project description:Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder triggered by specific food antigens, characterized by eosinophil-rich multicellular inflammation and structural changes in the epithelium. Treatment options for EoE include dietary therapy, pharmacological therapy, or a combination of both, chosen based on the patient's preference and clinical progression. Pharmacological options include proton pump inhibitors (PPIs), corticosteroids, and biologic therapy. Although PPI therapy is used for EoE management, its underlying mechanism of action remains unclear. To investigate the effects of omeprazole, an orally bioavailable PPI commonly used for EoE therapy, on the dynamics of esophageal epithelial barrier function and inflammation, we employed air-liquid interface (ALI) culture. We examined how omeprazole affects gene expression changes caused by IL-13 treatment. ALI cultures were treated with 100 ng/ml of IL-13 and/or 50 µM of acid-activated omeprazole for 96 hours, and bulk RNA sequencing was performed to analyze the epithelial-specific transcriptomes of IL-13 and/or omeprazole-treated ALI. Our findings suggest potential gene interactions where omeprazole may mitigate transcriptional changes induced by IL-13, indicating that omeprazole may attenuate IL-13 mediated epithelial dysfunction relevant to EoE pathophysiology by modulating pathways associated with inflammation, tissue repair, and cell-cell communication.
2024-09-13 | GSE273039 | GEO
Project description:Eosinophilic esophagitis (EoE) is an immune-mediated disease triggered by food antigens for which dietary elimination treatment can induce and sustain histologic remission. Our review aims to describe the state of the art regarding dietary treatment of EoE, highlighting a number of areas of controversy related to dietary therapy in EoE, including novel modalities for determining food triggers, making the empiric dietary elimination process more efficient, issues of cross-contamination and "dosing" of how much food to avoid or add back, costs and effects on quality of life, long-term efficacy, and the risk of developing immediate IgE-type reactions after initial dietary elimination. Elemental formulas, empiric elimination diets, and targeted allergy test-directed elimination diets are well-described treatments for EoE. Although elemental diets are most efficacious, their clinical use is limited by cost and the palatability of an exclusively liquid diet. While empiric elimination is less effective than elemental formula-based diets, they are more easily implemented and often sustainable. Since the comparative effectiveness of elimination diets with proton-pump inhibitors and swallowed topical steroids remains unknown, there are multiple areas to address with future research.
| S-EPMC6532639 | biostudies-literature
Project description:ObjectivesEosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.MethodsThis prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.ResultsWe found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein (P < 0.05) and a significant increase in filaggrin levels after PPI treatment (P < 0.01).ConclusionsEsophageal miRNA levels found are able to discriminate between both PPI-R and PPI-NR at baseline, and before and after treatment in PPI-R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI-R patients after PPI therapy.
| S-EPMC7752232 | biostudies-literature
Project description:Purpose of reviewManagement for patients with refractory eosinophilic esophagitis (EoE) remains a clinical challenge. This review aims to define refractory EoE, explore rates and reasons for nonresponse, and discuss the evidence that informs the approach to these patients.Recent findingsMany patients will fail first-line therapies for EoE. Longer duration of therapy can increase response rates, and initial nonresponders may respond to alternative first-line therapies. There are ongoing clinical trials evaluating novel therapeutics that hold promise for the future of EoE management. Increasingly, there is recognition of the contribution of oesophageal hypervigilance, symptom-specific anxiety, abnormal motility and oesophageal remodelling to ongoing clinical symptoms in patients with EoE.SummaryFor refractory EoE, clinicians should first assess for adherence to treatment, adequate dosing and correct administration. Extending initial trials of therapy or switching to an alternative first-line therapy can increase rates of remission. Patients who are refractory to first-line therapy can consider elemental diets, combination therapy or clinical trials of new therapeutic agents. Patients with histologic remission but ongoing symptoms should be evaluated for fibrostenotic disease with EGD, barium esophagram or the functional luminal imaging probe (FLIP) and should be assessed for the possibility of oesophageal hypervigilance.
| S-EPMC9552275 | biostudies-literature
Project description:ObjectivesDietary elimination for treatment of eosinophilic esophagitis (EoE) is limited by lack of accuracy in current allergy tests. We aimed to develop an immunologic approach to identify dietary triggers and prospectively test allergen-specific immune signature-guided dietary elimination therapy.MethodsIn the first phase, we developed and assessed 2 methods for determining selected food triggers using samples from 24 adults with EoE: a CD4+ T-cell proliferation assay in peripheral blood and food-specific tissue IgG4 levels in esophageal biopsies. In the second phase, we clinically tested elimination diets created from these methods in a prospective cohort treated for 6 weeks (NCT02722148). Outcomes included peak eosinophil counts (eos/hpf), endoscopic findings (measured by the EoE Endoscopic Reference Score), and symptoms (measured by the EoE Symptom Activity Index).ResultsParameters were optimized with a positive test on either assay, yielding agreements of 60%, 75%, 53%, 58%, and 53% between predicted and known triggers of peanut, egg, soy, wheat, and milk, respectively. In clinical testing, the mean number of foods eliminated based on the assays was 3.4, and 19 of 22 subjects were compliant with treatment. After treatment, median peak eosinophil counts decreased from 75 to 35 (P = 0.007); there were 4 histologic responders (21%). The EoE Endoscopic Reference Score and EoE Symptom Activity Index score also decreased after treatment (4.6 vs 3.0; P = 0.002; and 32.5 vs 25.0; P = 0.06, respectively).DiscussionWe successfully developed a new testing approach using CD4 T-cell proliferation and esophageal food-specific IgG4 levels, with promising accuracy rates. In clinical testing, this led to improvement in eosinophil counts, endoscopic severity, and symptoms of dysphagia, but a smaller than expected number of patients achieved histologic remission.
| S-EPMC6970559 | biostudies-literature
Project description:OBJECTIVE:Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). METHODS:Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. RESULTS:Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C1917 (P = 0.35). In children who received a PPI dose between ?1.54 and ?2.05?mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C1917 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C1917 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P?=?0.022; CYP2C1917 OR [95% CI]?=?8.19[1.42, 50.57], P = 0.023). CONCLUSIONS:Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.
| S-EPMC6855320 | biostudies-literature
Project description:Topical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE).We aimed to summarize published manuscripts that report outcomes of these therapies for EoE.We performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis.Systematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2-96.0%] for fluticasone, 76.8% (95% PL 36.1-95.1%) for budesonide, and 69.0% (95% PL 31.9-91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0-56.7), 62.5 (95% PL 125.6 to -0.67, and 44.6 (95% PL 26.5-62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1-91.1%), 87.9% (95% PL 42.7-98.6%), and 87.3% (95% PL 64.5-96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations' baseline eosinophil count and age.The literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.
| S-EPMC5709168 | biostudies-literature
Project description:Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective.We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics.In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive.In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life.
| S-EPMC5440206 | biostudies-literature