A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time.

INTRODUCTION: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined. METHODS: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls. RESULTS: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months). DISCUSSION: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.

Barrett's Esophagus in Eosinophilic Esophagitis in Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

INTRODUCTION: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. METHODS: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients. RESULTS: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). CONCLUSION: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy.

Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice - International Expert Recommendations.

BACKGROUND & AIMS: There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor patients with EoE in routine clinical practice, on the basis of available clinical evidence and expert opinion. METHODS: A multidisciplinary, international group of EoE experts identified the following important 3 questions during several consensus meetings: why, by what means, and when to monitor patients with EoE. A steering committee was named, and 3 teams were formed to review literature and to formulate statements for each topic. In a Delphi survey, a level of agreement of ≥75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed, and statements were rephrased/rewritten if necessary. RESULTS: Eighteen EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university-based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring patients with EoE. Each statement attained ≥75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. CONCLUSIONS: It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured, and, under certain conditions, individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side effects, adjusting therapy, and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.

Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference.

Endoscopy plays a critical role in caring for and evaluating the patient with eosinophilic esophagitis (EoE). Endoscopy is essential for diagnosis, assessment of response to therapy, treatment of esophageal strictures, and ongoing monitoring of patients in histologic remission. To date, less-invasive testing for identifying or grading EoE severity has not been established, whereas diagnostic endoscopy as integral to both remains the criterion standard. Therapeutic endoscopy in patients with adverse events of EoE may also be required. In particular, dilation may be essential to treat and attenuate progression of the disease in select patients to minimize further fibrosis and stricture formation. Using a modified Delphi consensus process, a group of 20 expert clinicians and investigators in EoE were assembled to provide guidance for the use of endoscopy in EoE. Through an iterative process, the group achieved consensus on 20 statements yielding comprehensive advice on tissue-sampling standards, gross assessment of disease activity, use and performance of endoscopic dilation, and monitoring of disease, despite an absence of high-quality evidence. Key areas of controversy were identified when discussions yielded an inability to reach agreement on the merit of a statement. We expect that with ongoing research, higher-quality evidence will be obtained to enable creation of a guideline for these issues. We further anticipate that forthcoming expert-generated and agreed-on statements will provide valuable practice advice on the role and use of endoscopy in patients with EoE.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis.

BACKGROUND AND AIMS: Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. METHODS: Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). RESULTS: The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. CONCLUSIONS: EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.

Management of eosinophilic esophagitis associated food impaction in Europe and the United States.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge-The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings-Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

Sex Impacts Disease Activity But Not Symptoms or Quality of Life in Adults With Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis has a strong male predominance that appears at least partially due to genetic susceptibility. However, data regarding sex-related differences in patients with EoE are scarce. METHODS: We analyzed prospectively collected data from adults enrolled into the Swiss Eosinophilic Esophagitis Cohort Study. Patients with and without dilation in the past 12 months completed patient-reported Eosinophilic Esophagitis Activity Index (EEsAI) and EoE-specific quality of life in adults (EoE-QoL-A) and underwent endoscopy with biopsies. We used linear regression with EEsAI or EoE-QoL-A as the outcome, eosinophils per high power field, rings and strictures, current therapy use, and disease duration as predictors. RESULTS: A total of 266 patients (77% male, median age at diagnosis 35.8 years, median disease duration 10.4 years) were seen during 408 visits. Men had a longer diagnostic delay (62 months vs 36 months; P = .022), higher endoscopic disease activity (median endoscopic reference score 3.0 [interquartile range, 1.0-6.0] vs 2.0 [interquartile range, 0.0-4.0]; P = .010), more microabscesses (25% vs 13%; P = .025), and more often fibrosis of the lamina propria (mild/moderate 74.7% vs 61.5%, severe 9.1% vs 5.8%; P = .047) than women. When adjusting for objective measures of disease activity, disease duration, and current therapy use, we did not observe differences in EEsAI or EoE-QoL-A between women and men. CONCLUSIONS: Male EoE patients had higher endoscopic and histologic disease activity than female patients. When adjusting for biologic activity and therapy use, we did not identify differences in symptom severity or EoE-QoL between male and female eosinophilic esophagitis patients.

Clinicopathologic Correlations in Eosinophilic Gastrointestinal Disorders.

Eosinophilic gastrointestinal disorders (EGIDs) are a collection of disorders characterized by allergy-driven inflammation of the gastrointestinal (GI) tract. Affected patients typically present with nonspecific symptoms of GI dysfunction and are frequently found to have mucosal abnormalities during endoscopy as well as increased eosinophil levels on tissue biopsy that are felt to be responsible for generating the clinical findings. Each of these findings is important in both the diagnosis and management of EGIDs. Understanding the impact of histopathologic and endoscopic changes on clinical signs and symptoms is critical to developing an understanding of the natural history of these disorders as well as to the generation of validated assessment tools and targeted therapies. We explore these relationships in this review.

Technical feasibility, clinical effectiveness, and safety of esophageal stricture dilation using a novel endoscopic attachment cap in adults with eosinophilic esophagitis.

BACKGROUND AND AIMS: The BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) is a new device that allows optical and tactile feedback during stricture dilation of the upper GI tract. We evaluated the technical feasibility, clinical efficacy, and safety of a 1-time esophageal stricture dilation using the BougieCap in adults with eosinophilic esophagitis (EoE). METHODS: EoE patients prospectively included in the Swiss EoE Cohort were dilated with the BougieCap for esophageal strictures (esophageal diameter, ≤14 mm) and stricture-related symptoms. Symptoms were assessed before and 2 weeks after a single dilation session using the validated Eosinophilic Esophagitis Activity Index Patient Reported Outcomes instrument (score ranges from 0 to 100 points). RESULTS: Fifty patients (70% men; median age, 41 years; median disease duration, 4 years; 50% treated with swallowed topical corticosteroids, 10% with proton pump inhibitors, 14% with combined swallowed topical corticosteroids plus proton pump inhibitors, 14% with elimination diet, 12% without antieosinophil therapy) were evaluated. Endoscopic bougienage was technically successful in 100%. The median esophageal diameter increased from 12 mm (interquartile range [IQR], 12-13) to 16 mm (IQR, 16-16; P < .001). Median symptom severity dropped from 32 points (IQR, 27-41) to 0 (IQR, 0-10; P < .001) at 2 weeks postdilation. In 1 patient the BougieCap was temporarily lost after stricture dilation in the hypopharynx but could be retrieved. No severe adverse events were reported. CONCLUSIONS: In adults with EoE, endoscopic treatment of esophageal strictures using the BougieCap is technically feasible and safe and offers significant symptomatic improvement in the short term.

Long-term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: The short-term efficacy of RPC4046, a monoclonal antibody against interleukin-13, has been shown in patients with eosinophilic esophagitis (EoE). We investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE. METHODS: We analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. The study was conducted at 28 centers in 3 countries; patients were enrolled between September 2014 and January 2017. Outcomes were stratified by double-blind dose group and included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety. RESULTS: By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores did not differ considerably between patients who originally received placebo vs RPC4046. Most patients maintained responses through week 52. Symptom remission (symptom-based EoE activity index score, ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo‒RPC4046 patients and from 30% to 54% in RPC4046‒RPC4046 (either dose) patients. Of the 28 patients who did not have a histologic response to RPC4046 during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%). CONCLUSIONS: One year of treatment with RPC4046 is generally well tolerated and results in continued improvement and/or maintenance of endoscopic, histologic, and clinical measures of EoE disease activity relative to baseline. TRIAL REGISTRATION: NCT02098473.

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

BACKGROUND & AIMS: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission. METHODS: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse. RESULTS: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected. CONCLUSION: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.

How to approach adult patients with asymptomatic esophageal eosinophilia.

As the awareness among gastroenterologists regarding endoscopic features suggesting eosinophilic esophagitis is increasing, individuals without symptoms of esophageal dysfunction are increasingly being found to have esophageal eosinophilia on biopsies performed during upper gastrointestinal endoscopies. However, the course of disease and the management of these asymptomatic individuals with esophageal eosinophilia remain elusive. In this review, we propose a definition of asymptomatic individuals with esophageal eosinophilia and discuss the prevalence, risk factors, and course of disease of this specific patient group. Furthermore, we have established a diagnostic and therapeutic pathway based on the most recent available data.

Impact of obesity on disease activity and disease outcome in inflammatory bowel disease: Results from the Swiss inflammatory bowel disease cohort.

OBJECTIVE: The purpose of this study was to investigate the impact of obesity on disease activity and disease outcome in patients with inflammatory bowel disease. PATIENTS AND METHODS: The impact of obesity on inflammatory bowel disease disease activity and outcome was retrospectively assessed in 3075 patients enrolled in the prospective nation-wide Swiss inflammatory bowel disease cohort between July 2006 and September 2018. Baseline characteristics, disease activity and disease course in 325 obese inflammatory bowel disease patients (body mass index ≥30 kg/m2) were compared to 1725 normal weight inflammatory bowel disease individuals (body mass index 18.5-24.9). RESULTS: Among 3075 patients in the prospective Swiss inflammatory bowel disease cohort, 325 patients (10.6%) were obese, namely, 194 Crohn's disease patients, 131 ulcerative colitis, and inflammatory bowel disease-unclassified patients. Disease activity scores were elevated in obese Crohn's disease (Crohn's Disease Activity Index 33 vs 20, p = 0.001), but not ulcerative colitis patients. Obese Crohn's disease, but not ulcerative colitis patients were less likely to be in remission based on a Crohn's Disease Activity Index less than 100 and a calprotectin less than 100 ug/g. In a multivariate regression model, obesity was negatively associated with disease remission in Crohn's disease (odds ratio 0.610, 95% confidence interval 0.402-0.926, p = 0.020), but not ulcerative colitis. Increased soft stool frequency was observed in both obese Crohn's disease and ulcerative colitis patients. Adjusted Cox regression models revealed increased risk of complicated disease course in obese Crohn's disease patients (hazard ratio 1.197, 95% confidence interval 1.046-1.370, p = 0.009). No association between obesity and disease progression, index treatment failure was seen neither in Crohn's disease nor ulcerative colitis. CONCLUSION: Obesity is associated with decreased rates of disease remission and increased risk of complicated disease course in Crohn's disease over a six-year follow-up period. No effects were seen on disease progression and index treatment failure neither in Crohn's disease nor ulcerative colitis.

A novel proangiogenic B cell subset is increased in cancer and chronic inflammation.

B cells contribute to immune responses through the production of immunoglobulins, antigen presentation, and cytokine production. Several B cell subsets with distinct functions and polarized cytokine profiles have been reported. In this study, we used transcriptomics analysis of immortalized B cell clones to identify an IgG4+ B cell subset with a unique function. These B cells are characterized by simultaneous expression of proangiogenic cytokines including VEGF, CYR61, ADM, FGF2, PDGFA, and MDK. Consequently, supernatants from these clones efficiently promote endothelial cell tube formation. We identified CD49b and CD73 as surface markers identifying proangiogenic B cells. Circulating CD49b+CD73+ B cells showed significantly increased frequency in patients with melanoma and eosinophilic esophagitis (EoE), two diseases associated with angiogenesis. In addition, tissue-infiltrating IgG4+CD49b+CD73+ B cells expressing proangiogenic cytokines were detected in patients with EoE and melanoma. Our results demonstrate a previously unidentified proangiogenic B cell subset characterized by expression of CD49b, CD73, and proangiogenic cytokines.

Eosinophilic Gastroenteritis: Clinical Manifestation, Natural Course, and Evaluation of Treatment with Corticosteroids and Vedolizumab.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare, chronic inflammatory condition of the gastrointestinal tract. Little is known about its natural history and treatment outcomes. The aims of our analysis were to describe clinical presentation, response to current medical treatments, and to evaluate the response of refractory EGE to anti-integrin therapy. METHODS: Patients with confirmed diagnosis of EGE fulfilling the diagnostic criteria: (1) the presence of gastrointestinal symptoms, (2) dense eosinophilic infiltration of the gastrointestinal mucosa, and (3) exclusion of other conditions leading to gastrointestinal eosinophilia were included in this analysis. In patients non-responding to corticosteroids and/or anti-TNF treatment the integrin blocker vedolizumab was used. RESULTS: EGE patients (n = 22) were predominantly female (63%) with a median age at diagnosis of 41.5 years. The most frequent symptoms were abdominal pain (100%), diarrhea (59%), nausea/vomiting (36%), and bloating (27%). No pathognomonic endoscopic alterations were found. Eosinophilic infiltration was observed in the majority of patients in more than one segment. Patients were treated with systemic steroids, topical, and enteral release steroids in 21/22 (95%) patients, proton pump inhibitors in 7/22 (32%), TNFα inhibitors in 3/22 (14%), and vedolizumab in 4/22 (18%) patients. In 3/4 of steroid-refractory patients vedolizumab induced a clinical and histological improvement. CONCLUSIONS: The combination of highly variable clinical presentation, subtle endoscopic abnormalities, and involvement of several GI segments undermines the difficulty to diagnose EGE and the need for structured biopsy sampling. Corticosteroids were efficient in the majority of patients to induce remission. Response to the integrin blocker vedolizumab suggests further assessment in refractory cases.

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

Maintenance Treatment Of Eosinophilic Esophagitis With Swallowed Topical Steroids Alters Disease Course Over A 5-Year Follow-up Period In Adult Patients.

BACKGROUND & AIMS: Although swallowed topical corticosteroids (STCs) are effective in inducing remission of active eosinophilic esophagitis (EoE), there are few data on maintenance of long-term remission. We evaluated the long-term effectiveness of STC therapy for adults with EoE. METHODS: We performed a retrospective study using the Swiss EoE database. We analyzed data on 229 patients with EoE treated with STCs (175 male; mean age at diagnosis, 39±15 years; median time until diagnosis, 6 years) from 2000 through 2014. Patients were followed for a median of 5 years (interquartile range [IQR], 3-7 years). We collected data from 819 follow-up visits on clinical, endoscopic and histological disease characteristics. The primary endpoint was proportions of clinical, endoscopic, and histological remission in all patients and groups, based on the status and duration of STC treatment. RESULTS: Patients were taking STCs at 336 of the follow-up visits (41.0% of visits). The median duration of STC use before a follow-up visit was 347 days (IQR, 90-750 days) corresponding to 677 doses (IQR, 280-1413 doses) of 0.25 mg each. At the visits, higher proportions of patients who were still taking STCs were in clinical remission (31.0%) compared to patients not taking STCs (4.5%) (P <.001), as well as endoscopic remission (48.8% vs 17.8%; P < .001), histologic remission (44.8% vs 10.1%; P < .001), and complete remission (16.1% vs 1.3%; P < .001). Higher cumulative doses of STCs and longer durations of treatment were associated with higher proportions of clinical and complete remission. No dysplasia or mucosal atrophy was detected. Esophageal candidiasis was observed at 2.7% of visits in patients taking STCs. CONCLUSION: In an analysis of data from the Swiss EoE database, we found maintenance therapy with STCs to achieve complete remission at 16.1% of follow-up visits, which was higher than in patients receiving no treatment (1.3%). Given the good safety profile of low-dose STC, we advocate for a prolonged treatment. Dose-finding trials are needed to achieve higher remission rates.