Treatment Of Eosinophilic Esophagitis Research Articles

Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles. We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eos/HPF in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens. A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian. Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE.

Eosinophilic Esophagitis: The Role of Steroids and the Dose, Duration, and Delivery of Steroid Therapy.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition characterized by the eosinophil infiltration of the esophagus (>15 per high power field). Recently, there has been an increase in both the incidence and prevalence of the disease. The common modalities of treatment are dietary modification, proton pump inhibitors, and steroids. However, the United States Food and Drug Administration has not approved any drugs for the treatment of EoE. This review has discussed the role of steroids in the treatment of EoE, focusing on the various formulations of the drug, its dosage, drug delivery, and duration of therapy. The study also covers the common outcomes of steroid therapy and its side effects.

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

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies-the only accurate method of assessing PPI response-efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.

Single-food elimination of cow's milk as a treatment for eosinophilic esophagitis in children aged 2-18 years: A review of the literature.

Cow's milk elimination (CME) is an established treatment, similar to other forms of diet therapy, for eosinophilic esophagitis (EoE). However, there is limited research to support its efficacy as a primary treatment. This review evaluated studies published in the past 10 years that assessed the outcomes after CME on histologic remission, clinical findings, and quality of life (QoL) in children aged 2-18 years with EoE. The evidence demonstrated that CME was effective at achieving histologic remission of disease in 50%-65% of children. This intervention also improved clinical symptoms seen on endoscopy and resulted in increased QoL when self-reported by children. CME can be used as a primary treatment for some children with EoE.

Understanding of Eosinophilic Esophagitis in Children - A Comprehensive Study on Epidemiology, Clinical Manifestations, Diagnosis and Innovative Treatment Modalities

Introduction:&#x0D; In the late 1960s, probable cases of eosinophilic esophagitis (EoE) emerged, initially linked to esophageal rings and congenital causes or gastroesophageal reflux disease (GERD). Doubts about the GERD association arose due to poor responses to antisecretory therapy. EoE is now a significant pediatric health concern, impacting 1 to 7 cases per 10,000 children.&#x0D; Purpose of the Study:&#x0D; This study aims to comprehensively explore EoE's epidemiology, etiology, subtypes, clinical manifestations, diagnostic methods, and treatment modalities.&#x0D; Materials and Methods:&#x0D; The study employs a cross-sectional analysis of pediatric EoE patients, utilizing endoscopic evaluation and histological assessment. Three distinct EoE subtypes are identified based on pathogenic characteristics. Clinical manifestations, diagnostic methods, and treatments, including endoscopy, are examined.&#x0D; Results:&#x0D; Clinical manifestations span a broad spectrum in the pediatric population. Diagnostic methods include endoscopy, esophageal manometry, impedance-pH monitoring, capsule endoscopy, and string tests. Three distinct EoE subtypes are identified with unique characteristics. Treatment modalities involve dietary management, proton pump inhibitors, topical corticosteroids, biologic therapies, allergen immunotherapy, and endoscopic interventions.&#x0D; Conclusion:&#x0D; Formerly associated with GERD, EoE is now a significant pediatric health concern. The study underscores the importance of comprehensive diagnostic approaches and diverse treatment modalities, including promising biologic therapies and allergen immunotherapy. Understanding these aspects is crucial for effective management and improved outcomes in patients.

There is a long way from current clinical practice in Denmark compared to recent published English guideline on management of children with eosinophilic oesophagitis

BackgroundA low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007–2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease.ObjectiveThe aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN).MethodsThis retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007 and 2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected.ResultsIn 32% of the children with EoE in the NDR, first-line treatment corresponded with the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Histologic evaluation within 12 weeks as recommended was performed in 13% of the children.ConclusionsIn Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline.

Dupilumab: a novel treatment for eosinophilic esophagitis

Dupilumab: a novel treatment for eosinophilic esophagitis

Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE?

PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.

Biologics in the Treatment of Eosinophilic Esophagitis: Ready for Use?

Biologics in the Treatment of Eosinophilic Esophagitis: Ready for Use?

TSLP shapes the pathogenic responses of memory CD4+ T cells in eosinophilic esophagitis.

The cytokine thymic stromal lymphopoietin (TSLP) mediates type 2 immune responses, and treatments that interfere with TSLP activity are in clinical use for asthma. Here, we investigated whether TSLP contributes to allergic inflammation by directly stimulating human CD4+ T cells and whether this process is operational in eosinophilic esophagitis (EoE), a disease linked to variants in TSLP. We showed that about 10% of esophageal-derived memory CD4+ T cells from individuals with EoE and less than 3% of cells from control individuals expressed the receptor for TSLP and directly responded to TSLP, as determined by measuring the phosphorylation of STAT5, a transcription factor activated downstream of TSLP stimulation. Accordingly, increased numbers of TSLP-responsive memory CD4+ T cells were present in the circulation of individuals with EoE. TSLP increased the proliferation of CD4+ T cells, enhanced type 2 cytokine production, induced the increased abundance of its own receptor, and modified the expression of 212 genes. The epigenetic response to TSLP was associated with an enrichment in BATF and IRF4 chromatin-binding sites, and these transcription factors were induced by TSLP, providing a feed-forward loop. The numbers of circulating and esophageal CD4+ T cells responsive to TSLP correlated with the numbers of esophageal eosinophils, supporting a potential functional role for TSLP in driving the pathogenesis of EoE and providing the basis for a blood-based diagnostic test based on the extent of TSLP-induced STAT5 phosphorylation in circulating CD4+ T cells. These findings highlight the potential therapeutic value of TSLP inhibitors for the treatment of EoE.

Feeding Tube Placement, Complications, and Treatment Responses in a Large Eosinophilic Esophagitis Patient Population.

Feeding tubes can provide a temporary or long-term solution for nutritional therapy. Little is known regarding the use of feeding tubes in patients with eosinophilic esophagitis (EoE). We sought to describe the characteristics and outcomes in EoE patients requiring tube feeding. This was a retrospective cohort study of EoE patients at a large tertiary care health system. Demographics, clinical characteristics, and endoscopic findings were extracted from medical records, and patients who had a feeding tube were identified. Patients with and without a feeding tube were compared. Details about the tube, complications, and treatment were extracted. Growth, global symptomatic, endoscopic, and histopathologic (<15 eos/hpf) responses were compared before and after the initiation of feeding tube therapy. We identified 39 of 1216 EoE patients who had a feeding tube (3%). Feeding tube patients were younger (mean age 6.3 years), reported more vomiting, and had a lower total endoscopic reference score than non-feeding tube patients ( P < 0.01 for all). Tubes were used for therapy for an average of 6.8 years, with most patients (95%) receiving both pharmacologic and formula treatment for EoE. An emergency department visit for a tube complication was required in 26%. Tube feeding improved body mass index z score ( P < 0.01), symptomatic response (42%), endoscopic response (53%), and histologic response (71%). Among EoE patients, only a small subset required a feeding tube and predominantly were young children with failure to thrive. Feeding tubes significantly improved growth and, when used in combination with other treatments, led to reduced esophageal eosinophilic inflammation.

Novel corticosteroid formulations in the treatment of eosinophilic esophagitis: what is the evidence?

Eosinophilic esophagitis (EoE) is a food allergen-induced disease of the esophagus. Chronic, eosinophil-predominant inflammation eventually leads to fibrosis, esophageal dysfunction and severe morbidity. Swallowed topical corticosteroids (STCs) are a mainstay of anti-inflammatory therapy in the treatment of active EoE. Data on the efficacy of novel corticosteroid formulations, developed specifically for esophageal delivery, have recently become available. A comprehensive review was performed aiming to summarize evidence on the role of STCs in the treatment of EoE. Two biomedical bibliographic databases (PubMED, EMBASE) were searched for articles providing original information on the efficacy and safety of STCs in adult EoE patients. Budesonide orodispersible tablet (BOT) and budesonide oral suspension (BOS) both surpassed placebo formulations regarding the efficacy of inducing and maintaining histologic, symptomatic and endoscopic remission. Overall, BOT displayed the highest grade of efficacy with clinico-histologic remission rates up to 75% after 1 year. Fluticasone propionate (APT-1011) achieved and maintained histologic and endoscopic responses in the majority of patients, whereas only a positive trend was demonstrated for symptomatic improvement. Mometasone and ciclesonide were studied in a limited number of smaller-scale trials and placebo-controlled data are required to substantiate the promising findings. All STCs displayed a similar side effects profile and were generally considered safe and well-tolerated. Current evidence supports long-term treatment with novel corticosteroid formulations, challenging the established treatment paradigm of EoE. BOT appears to be the most effective steroid therapy, although head-to-head comparative trials between STCs are needed.

Recent Advances in the Treatment of Eosinophilic Esophagitis

Recent Advances in the Treatment of Eosinophilic Esophagitis

Recent Advances in the Treatment of Eosinophilic Esophagitis.

Eosinophilic esophagitis is an increasingly common inflammatory allergic disease of the esophagus characterized by esophageal eosinophilia and symptoms of esophageal dysfunction. The therapeutic landscape has rapidly evolved for this emerging type 2 inflammatory disorder. We review traditional therapies including updates and expert opinions in addition to promising therapies on the horizon and the history of therapies that failed to meet end points and highlight knowledge gaps for future investigations.

142. EFFECTS OF PPIS AND P-CAB ON RESPONSES ACCORDING TO OUTCOMES OF SYMPTOM, ENDOSCOPY, AND HISTOLOGY IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS

Abstract Background and Aim Acid-suppressive drugs such as proton pump inhibitors and potassium-competitive acid blockers (PPIs/P-CABs) are often used to treat eosinophilic esophagitis (EoE). Treatment response is based on outcomes including, symptoms, endoscopy, and histology; however, the detailed response rate to PPI/P-CAB is unknown. We aimed to examine the response rate to PPIs/P-CABs and prevalence of topical corticosteroid (TCS) therapy as the second-line treatment for EoE, and compare efficacy between PPIs and P-CAB. Methods In total, 236 patients with histologically confirmed EoE who received PPI/P-CAB as the first-line treatment were included. We assessed the symptoms, endoscopic reference score (EREFS), and histology (eosinophils per high-power field, eos/hpf) 8 weeks after PPI/P-CAB administration. Complete normalization was defined as disappearance of symptoms, EREFS score 0, or 0–1 eos/hpf and response as disappearance or improvement of symptoms, EREFS score ≤ 2, or &amp;lt; 15 eos/hpf. The prevalence of TCS therapy in each response group was assessed. Results Complete normalization of PPI/P-CAB was achieved in 25%, 50%, 36%, and 8% of patients for symptoms, endoscopy, histology, and all three outcomes, respectively. The response rates of PPI/P-CAB were 81%, 87%, 87%, 75%, and 60% for symptoms, endoscopy, histology, and all three outcomes, respectively. There were no significant differences in compete normalization and response rate of any outcomes between PPIs and P-CAB. TCS use was significantly lower (8%) in patients who achieved response of all three outcomes than in other groups, and was dependent on the number of outcomes with non-response. Conclusions Complete normalization of symptoms, endoscopy, and histology using PPI/P-CAB is uncommon. Based on treatment efficacy by response/non-response, TCS was the secondary treatment in cases with an increase in the number of non-response outcomes. Treatment efficacy of PPIs and P-CAB was similar.

Predictors of histologic response to mepolizumab in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus. Current treatment options are limited. One experimental therapy is antibodies against interleukin-5 (IL-5). However, it is unknown why some patients respond to anti-IL-5 treatment whereas others do not. We sought to delineate predictors of histologic response to anti-IL-5 therapy in pediatric EoE. This post hoc analysis of a multicenter, double-blind clinical trial (ClinicalTrial.gov identifier: NCT00358449) evaluated mepolizumab for the treatment of EoE in pediatric patients. Predictors were assessed for their association with a histologic response at week 12 of treatment. A histologic response was defined as either <15 eosinophils per hpf or a reduction in peak eosinophil counts by ≥50%. Predictors on univariate analysis with P < 0.10 were included in multivariate logistic regression models. Statistical significance for multivariate comparisons was set at P < 0.05. Patients with a higher BMI were more likely to attain histologic response at week 12, defined as <15 eosinophils per hpf [aOR, 1.31; 95% confidence interval (CI), 1.07-1.60; P = 0.008]. Higher BMI (aOR, 1.70; 95% CI, 1.06-2.74; P = 0.029) and signs of exudate plaques on endoscopy (aOR, 18.30; 95% CI, 2.11-158.53; P = 0.008) were significant predictors of histologic response at week 12 where a histologic response was defined as a reduction in peak eosinophil counts by ≥50. Higher BMI and signs of exudative plaques on endoscopy may be predictors of histologic response in pediatric EoE patients treated with antibodies against IL-5. Further studies are needed to validate our findings.

Validation of Epigenetic Markers for the Prediction of Response to Topical Corticosteroid Treatment in Eosinophilic Esophagitis.

We previously identified 18 CpG methylation biomarkers associated with treatment response to topical corticosteroids (tCS) in eosinophilic esophagitis (EoE). In this study, in an independent cohort, we assessed the validity of these CpG sites as treatment response biomarkers. DNA was extracted from prospectively biobanked esophageal biopsies from patients with newly diagnosed EoE enrolled in a randomized trial of 2 tCS formulations. Histologic response was defined as <15 eosinophils per high-power field. Pretreatment DNA methylation was assayed on the Illumina Human MethylationEPIC BeadChip. Logistic regression and area under the receiver operating characteristic curve analyses, adjusting for chip, position on the chip, age, sex, and baseline eosinophil count, were computed to test for an association between DNA methylation and treatment response at the 18 previously identified CpG sites. We analyzed 88 patients (58 histologic responders, 30 nonresponders), with a mean age of 38 ± 16 years, 64% male, 97% White race. Of the 18 CpG sites, 13 met quality control criteria, and 3 were associated with responder status ( P < 0.012), including sites within UNC5B (cg26152017), ITGA6 (cg01044293), and LRRC8A (cg13962589). All 3 showed evidence of reduced methylation in treatment responders, consistent with the original discovery associations. The predictive probability for nonresponse with all 3 CpG sites was strong (area under the receiver operating characteristic curve = 0.79). We validated epigenetic biomarkers (CpG methylation sites) for the prediction of tCS response in patients with EoE in an independent population. While not all previously identified markers replicated, 3 demonstrated a relatively high predictive probability for response to treatment and hold promise for guiding tCS treatment in EoE.

Diagnosis of Eosinophilic Esophagitis at the Time of Esophageal Food Impaction.

Esophageal food impactions (EFI) often precede a diagnosis of eosinophilic esophagitis (EOE). Current guidelines suggest obtaining esophageal biopsies upon suspicion of EOE, treating with proton pump inhibitor (PPI), and repeating esophagogastroduodenoscopy (EGD). This study was conducted to determine provider practice patterns with these mentioned recommendations at the time of EFI. In this retrospective study, key outcomes were the proportion of patients who had EOE mucosal biopsies, EOE diagnosis, PPI initiation, and recommendations and completions of repeat EGD. Differences in outcomes among age, sex, race, off-hours time of procedure, and trainee involvement were examined. EOE diagnosis predictors were explored with logistic regression. Twenty-nine percent of the patients had esophageal biopsies taken at the time of index EGD (iEGD). Sixteen patients were diagnosed with EOE at the time of index EFI, while fourteen patients were diagnosed on subsequent EGDs. Among those diagnosed with EOE at iEGD, 94% were placed on PPI. Of patients with confirmed EOE on index biopsy, 63% of patients were recommended repeat EGD, of which 50% completed it within 90 days. Older age was protective of EOE diagnosis while no GERD history and endoscopist suspicion of EOE predicted diagnosis of EOE. Endoscopists uncommonly take biopsies at the time of EFI, which may delay diagnosis and treatment of EOE.

Variability in Swallowed Topical Corticosteroid Practice Patterns for Treatment of Pediatric Eosinophilic Esophagitis.

Given the variety of preparations and lack of standardization of swallowed topical corticosteroids (STC) for treatment of eosinophilic esophagitis (EoE), we sought to better understand STC prescribing practices of pediatric gastroenterologists. A 12-question survey was distributed to members of NASPGHAN Eosinophilic Gastrointestinal Disease Special Interest Group (EGID SIG) and responses were analyzed. Forty-two of 68 physicians responded. Oral viscous budesonide (OVB) was overall first choice STC in 31 (74%) survey respondents, with OVB most frequently utilized in patients under 5 years-old and fluticasone propionate (FP) in patients 13-18 years-old. Nineteen types of mixing vehicles were used for OVB preparation, the three most frequent being sucralose, honey, and artificial maple syrup. Insurance coverage, cost, and patient compliance were most frequently cited barriers to STC use. Highly variable STC prescribing practices reported by this group highlights the need for standardization of STC treatment in EoE.

Treatment of eosinophilic esophagitis - advancements and perspectives

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.