Treatment Of Eosinophilic Esophagitis Research Articles

Platelet association with leukocytes in active eosinophilic esophagitis

We previously demonstrated that the percentage of blood eosinophils that are associated with platelets and thus positive for CD41 (integrin αIIb-subunit) correlates with and predicts peak eosinophil count (PEC) in biopsies of eosinophilic esophagitis (EoE) patients after treatment. Thus, flow cytometric determination of CD41+ eosinophils is a potential measure of EoE disease activity. Determinants of association of platelets with eosinophils and other leukocytes in EoE are largely unknown. The objectives of this study were to test the hypotheses that platelets associate with blood leukocytes other than eosinophils in EoE and that such associations also predict EoE activity. Whole blood flow cytometry was performed on samples from 25 subjects before and after two months of standard of care EoE treatment. CD41 positivity of cells within gates for eosinophils, neutrophils, monocytes, lymphocytes, and natural killer cells was compared. We found that percent CD41+ neutrophils, monocytes, and eosinophils correlated with one another such that principal component analysis of the five cell types identified “myeloid” and “lymphoid” factors. Percent CD41+ neutrophils or monocytes, or the myeloid factor, like CD41+ eosinophils, correlated with PEC after treatment, and CD41+ neutrophils or the myeloid factor predicted PEC < 6/high power field after treatment, albeit with lower area under the curve than for CD41+ eosinophils. We conclude that the processes driving platelets to associate with eosinophils in EoE also drive association of platelets with neutrophils and monocytes and that association of platelets with all three cell types is related to disease activity. Clinicaltrials.gov identifier: NCT02775045.

Obesity reduces the requirement for subsequent esophageal stricture dilation in adults with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) causes esophageal narrowing and strictures, but factors that modify the severity of strictures and requirement for subsequent dilation are not well described. The aim of this study was to identify characteristics that impact the need for repeat (> 1) esophageal dilations in EoE patients. This was a single center retrospective cohort study over a 12-year period (September 2005-October 2017). Patients were identified using ICD9, ICD10, and CPT codes for esophageal dilation, eosinophilic esophagitis, and esophageal obstruction. Data for EoE clinical characteristics, treatments, and BMI were extracted and correlated to the number of esophageal dilations and time elapsed between dilations. Of the 21 patients who met inclusion criteria, 11 (52%) had at least two dilations and 9 (43%) had three dilations. There was no differences baseline demographics between patients who needed ≥ 2 vs. those who needed one dilation. However, patients with a BMI > 30 had a significantly longer median time to second dilation compared to non-obese patients (4.9years vs. 1.8years; p = 0.027). Stratification by either high dose PPI or inhaled steroid use did not change this result. EoE patients with strictures who are obese have a reduced requirement for subsequent esophageal dilation. While the mechanism for this is not clear, increased attention of non-obese patients with fibrostenotic EoE is indicated as they are at higher risk for recurrent strictures.

Biologics in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the oesophagus whose incidence is on the rise. Despite maximal use of guideline-based therapies including food elimination diets and steroids, many patients remain symptomatic. This review serves to summarize safety and efficacy of monoclonal antibodies in treatment of EoE. There has been an increasing number of biologics under consideration for EoE and several that have undergone clinical trials. mAbs that target specific effectors involved in the disease may offer additional clinical and histologic benefit. In addition, they offer a more benign adverse effect profile than traditional therapies. Biologics for treatment of EoE may result in symptom and histologic improvement and has the potential to treat disease with minimal side effects.

Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.

In Esophageal Squamous Cells From Eosinophilic Esophagitis Patients, Th2 Cytokines Increase Eotaxin-3 Secretion Through Effects on Intracellular Calcium and a Non-Gastric Proton Pump

In upper airway cells, T helper 2 cytokines that signal through interleukin-4 (IL-4) receptor-α have been shown to stimulate eotaxin-3 secretion via a nongastric proton pump (ngH+,K+ATPase). To seek novel targets for eosinophilic esophagitis (EoE) treatments, we evaluated ngH+,K+ATPase expression in EoE squamous cells, and explored molecular pathways involved in eotaxin-3 secretion by IL-4 receptor-α signaling. ngH+,K+ATPase expression in EoE cells was evaluated by quantitative real-time polymerase chain reaction and Western blotting. IL-4-stimulated eotaxin-3 secretion was measured by enzyme-linked immunosorbent assay after treatment with omeprazole, SCH 28080 (potassium-competitive acid blocker), ethylene glycol-bis(β-aminoethyl)-N,N,N',N'-tetraacetoxymethyl ester (calcium chelator), 2-aminoethoxydiphenyl borate (inhibitor of endoplasmic reticulum calcium release), verapamil, and diltiazem (L-type calcium channel inhibitors). Intracellular calcium transients were measured by Fluo-4 fluorescence. Key experiments were confirmed in EoE primary cells and in RNA sequencing datasets from mucosal biopsies of patients with EoE and controls. EoE cells expressed ngH+,K+ATPase messenger RNA and protein. Omeprazole and SCH 28080 decreased IL-4-stimulated eotaxin-3 secretion. IL-4 increased intracellular calcium transients, and IL-4-stimulated eotaxin-3 secretion was blocked by ethylene glycol-bis(β-aminoethyl)-N,N,N',N'-tetraacetoxymethyl ester, 2-aminoethoxydiphenyl borate, verapamil, and diltiazem. The combination of omeprazole and verapamil suppressed IL-4-stimulated eotaxin-3 secretion more than either agent alone. EoE biopsies expressed higher ngH+,K+ATPase and exhibited more calcium signaling than controls. EoE cells express a nongastric proton pump that mediates T helper 2 cytokine-stimulated eotaxin-3 secretion. IL-4 induces calcium release from the endoplasmic reticulum and calcium entry via L-type calcium channels, increasing intracellular calcium that contributes to eotaxin-3 secretion by EoE cells. L-type calcium channel inhibitors block T helper 2 cytokine-stimulated eotaxin-3 secretion, suggesting a potential role for these agents in EoE treatment.

Sudden Chest Pain Due to Esophageal Intramural Dissection

Sudden Chest Pain Due to Esophageal Intramural Dissection

Reversibility of Endoscopic Features after Treatment for Eosinophilic Esophagitis.

PurposeThe prevalence and incidence of eosinophilic esophagitis (EoE) are increasing worldwide. Despite increased understanding of inflammatory pathogenesis, changes in endoscopic features after treatment of EoE have not been clearly described. We aimed to investigate the reversibility of endoscopic features of EoE after treatment.Materials and MethodsOut of 58 adult subjects who were diagnosed with EoE at the Yonsei University Health System from July 2006 to August 2019, we recruited 33 subjects (30 males; mean age: 42 years) whose pre-treatment and post-treatment endoscopic images were available. Endoscopic features included both inflammatory and fibrostenotic features. Exudate, edema, furrow, and crepe paper-like mucosa were classified as inflammatory features. Ring and stricture were classified as fibrostenotic features. We compared changes in endoscopic features after treatment for EoE.ResultsAfter treatment, clinical symptoms improved in all patients. The following endoscopic features were observed before treatment: furrow (81.8%), edema (90.9%), exudate (42.4%), ring (27.3%), crepe paper-like mucosa (15.2%), and stricture (3.0%). Endoscopic remission was achieved in 21 patients (63.6%). Inflammatory features were reversible (72.7%, p<0.001), whereas fibrostenotic features were not (10%, p=0.160). Exudate had resolved in 92.9% of patients, edema in 70% and furrow in 88.9%. Ring and stricture persisted in almost all of the patients (9/10) who had these endoscopic features before treatment.ConclusionWe outlined the reversibility of endoscopic inflammatory features of EoE. Fibrostenotic features were irreversible after esophageal remodeling in patients with EoE. However, further validation studies with long-term follow-up are needed.

Eosinophilic esophagitis. What diet? How to treat it? The point of view of a gastroenterologist working in a department of allergology

Eosinophilic esophagitis (EoE) belongs to a broad group of allergic gastrointestinal diseases. More narrowly, it is classified as an eosinophilic gastrointestinal disease and is its most common representative. Until recently, this disease was extremely rare, but the last 3 decades have seen a rapid increase in its prevalence to such an extent that in some recent studies it has been named the most common esophageal disease after reflux disease. EoE is an interdisciplinary disorder on the borderline between gastrointestinal and allergologic diseases, requiring cooperation of these two branches of medicine in diagnostics and treatment. Despite the development of medical science it remains a poorly known disease, difficult to diagnose and even more difficult to treat. Recent years have seen the emergence of new studies and guidelines, both American and European, that have radically changed our approach to the diagnosis and treatment of EoE.

Diagnosis and treatment of eosinophilic esophagitis

嗜酸性粒细胞性食管炎（EoE）是一种慢性、由过敏原触发、Th2细胞介导的食管疾病，其特点是食管嗜酸性粒细胞增多浸润为主的炎症进而引发临床上以食管功能障碍为主的症状。其治疗方法包括药物治疗、饮食治疗及食管扩张，简称“3D”治疗。由于该病是一种慢性疾病，所以多数需要长期治疗，以预防复发及并发症的出现。本文对近年来EoE诊断及治疗方法的相关临床进展进行阐述，提供最新的EoE诊断及疾病管理方式。.

Eosinophils and T cell surface molecule transcript levels in the blood differentiate eosinophilic esophagitis (EoE) from GERD

We recently rereported that blood mRNA levels of T cells and IgE receptors are the novel non-invasive biomarkers for eosinophilic esophagitis (EoE) with the aim to establish the panel of T cells and IgE receptor as the novel non-invasive biomarkers for EoE. In addition to earlier proposed cell surface molecules, we now added T cell receptor CXCR6 and eosinophils expressed cell surface molecules CD101 and CD274 mRNA levels. The mRNA levels of eosinophils cell surface molecule CD101 and CD274 and T cell receptor CXCR6, Vβ11, CD1d and chemokine CXCL16 levels were examined using the blood of normal, EoE and GERD patients. The analysis showed statistically significant induced mRNA levels of CD274, CD101 and reduced CXCR6 will be an additional molecule with respective 95%, 90% and 90% positive predictive value in between EoE and GERD patients. In brief, these additional data will be critical to establish a complete panel of earlier published TCRδ (95%), Jα18 (83%) and FCeRII (100%) non-invasive biomarker to monitor the EoE severity and treatment effect in EoE patients. In conclusion, we now propose both induced and reduced transcript levels of cell surface molecules of the cell surface molecules along with earlier reported molecules that will be useful for monitoring EoE status before and following treatment. Most importantly, the complete predictive non-invasive biomarker panel will also serve to differentiate EoE from GERD.

Eosinophilic esophagitis: from pathophysiology to management.

Eosinophilic esophagitis (EoE) incidence and prevalence have sharply increased in the last decade; so, the management of these patients is changing rapidly. Standard regimens as elimination diet, proton pump inhibitors and topical swallowed steroids are not able to achieve remission in all patients. Moreover, loss of efficacy and safety concerns for long-term medical treatments are rising questions. As for other chronic immune-mediated diseases, biologics have been evaluated for the treatment of EoE. Several targets in the Th2-mediated inflammatory cascade with eosinophilic mucosal infiltration, have been tested with alternating results. This review provides a comprehensive discussion of the available studies evaluating biologics in EoE and the possible future options most desirable for these patients.

PGI27 Systematic Review and Network Meta-Analysis: Topical Corticosteroids for Inducing Histological Remission in Eosinophilic Oesophagitis

Topical corticosteroids, comprised mainly of fluticasone multi-dose inhaler content swallowed or budesonide viscous solution (BVS), are the foundation of treatment for eosinophilic oesophagitis (EoE). Recently, a budesonide orodispersible tablet (BOT) has been approved for the treatment of EoE. Given the absence of direct comparisons, we evaluated the relative efficacy of BOT with other topical corticosteroid formulations for inducing histological remission in patients with EoE by a network meta-analysis (NMA). A systematic literature review was performed using MEDLINE and Embase up to August 1, 2019. Eligible studies comprised randomised controlled trials (RCTs) which evaluated adult patients with a diagnosis of active EoE treated with a topical corticosteroid in comparison to placebo or another topical corticosteroid. The outcome of interest was the proportion of patients achieving induction of histological remission defined as a peak oesophageal eosinophil count of <5 eosinophils/high-power field. Direct comparisons were made using the Mantel-Haenszel method and an NMA was performed using a fixed effects Bayesian framework with Markov Chain Monte Carlo simulations. A total of 6 trials (n=447 patients) were included in the quantitative summary. The NMA determined that BOT was associated with a higher odds of histological remission compared to BVS (odds ratio [OR]=4.9 [95% credible interval [CrI]=1.4, 19.1]), fluticasone (7.4 [1.7, 34.5]), nebulised swallowed budesonide (NSB) (25.0 [2.9, 247.2]) and placebo (387.6 [97.5, 2,275.6]). Similar findings were observed for direct comparisons. This NMA of RCTs suggest that BOT is significantly more likely to achieve histological remission in adult patients with EoE compared to BVS, fluticasone, and NSB.

Delayed hypersensitivity reaction to orodispersible budesonide in a case with eosinophilic esophagitis

BackgroundEosinophilic esophagitis (EoE) is a chronic inflammatory disease that has been known since the early 1990s. Swallowed topical corticosteroids (STC) belong to the therapeutic cornerstones. We describe a delayed hypersensitivity reaction to Jorveza®, a newly developed orodispersible budesonide tablet licensed for the treatment of eosinophilic esophagitis.Case presentationA 32-year-old Caucasian woman with EoE was newly treated with Jorveza®. Hours after the first intake, she felt a “strange pruritus” in the throat. This sensation worsened with each subsequent intake. On day 4 she developed oral mucosal symptoms (paresthesia of the tongue, sore and an itchy throat). Intraoral, throat and facial swellings, but no systemic reaction were observed. Patch testing using two commercial test series as well as the orodispersible budesonide tablet revealed a strong sensitization, proving a T cell mediated allergy to budesonide.ConclusionsOrodispersible budesonide is increasingly prescribed for the treatment of eosinophilic esophagitis. The development of oropharyngeal symptoms after initiating should alert the treating physician to the possibility of a hypersensitivity reaction.

Corticosteroids for Eosinophilic Esophagitis in Children: A Meta-analysis.

Treatment of eosinophilic esophagitis (EoE) is focused on dietary, pharmacologic, and endoscopic therapy options. Within the pharmacologic alternatives, topical corticosteroids are the most used, and a large number of studies evaluating their effectiveness have been published, requiring a new summary of evidence. To evaluate the histologic and clinical effectiveness of the use of corticosteroids in pediatric patients with a diagnosis of EoE. Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, Latin American and Caribbean Health Sciences Literature, and ClinicalTrials.gov (June 2019). We selected randomized controlled trials assessing corticosteroids versus a placebo or dietary treatment of EoE in children. Methodologic quality of evidence was evaluated by using the Cochrane Collaboration's risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system. The primary outcomes were clinical and histologic improvement. A total of 1655 studies were identified. Five studies were included (206 patients). Histologic response was 49.25% in the corticosteroids group and 4.16% in the placebo group (risk ratio 11.05 [confidence interval 3.8-32.15]; P < .0001). Symptomatic response was 33.6% in the corticosteroids group and 21.8% in the control group (risk ratio 1.62 [confidence interval 0.94-2.79]; P = .08). There were no major adverse effects. Heterogeneity of the diagnosis of EoE. Our review revealed favorable results of corticosteroids versus placebo, mainly in histologic response. More studies are needed, by using validated clinical scores, to obtain more reliable results.

S0382 Delay in Diagnosis for Patients With Eosinophilic Esophagitis: Patient-Reported Barriers

INTRODUCTION: Though good treatment options exist with high efficacy rates, a significant delay exists for appropriate diagnosis and treatment of eosinophilic esophagitis (EoE), which can have long-term consequences of esophageal inflammation. This study aimed to describe characteristics and clinical course of patients diagnosed with EoE at one academic institution and to examine patient-reported barriers to timely diagnosis and treatment for EoE. METHODS: Structured phone surveys were conducted among patients aged 18 and older who had been diagnosed with EoE at a large academic institution from January 2017 to March 2020, identified by associated endoscopic diagnosis. Further clinical characteristics including endoscopic findings were extracted from electronic health records. Qualitative evaluation of the open-ended survey questions regarding barriers to diagnosis and treatment included codebook development and thematic analyses. Descriptive statistics were conducted via SAS. RESULTS: Among 106 patients who met inclusion criteria, 41 completed structured phone surveys (age 47 ± 17, 61% male, 88% White). Of the responders, the mean age at symptom onset was 26 (±20) and the mean age at the time of diagnosis was 43 (±20); the calculated average time from symptom onset to seeking medical care was 51 (±80) months, symptom onset to diagnosis of EoE was 73 (±83) months, and symptom onset to treatment was 78 (±83) months. Dysphagia was the most commonly reported presenting symptom (61%), followed by food impaction (39%), reflux (27%), chest pain (10%), and nausea/vomiting (10%). Treatments reported included proton pump inhibitors (75%), inhaled steroids (46%), and food elimination (32%). All had at least one upper endoscopy: 46% of patients had findings of edema, 68% had rings, 37% had exudate, 49% had furrows, and 46% had strictures. Sixteen (39%) required dilation. At the time of survey, 60% reported that their EoE was “well controlled”, 36% “somewhat controlled”, and 5% “not controlled”. Salient themes in patient reported barriers included 1) delay in seeking care due to dismissal of symptoms (49%), 2) need for early referral to specialist/endoscopy (37%), and 3) lack of patient resources/understanding of disease resulting in nonadherence to recommended work-up or treatment (34%). CONCLUSION: Significant diagnostic and treatment delay persists for those with EoE. Patient-centered interventions that target barriers at various levels are needed to prevent long-term consequences.Table 1

S0380 Role of Biologic Agents in the Treatment of Eosinophilic Esophagitis: Literature Review

S0380 Role of Biologic Agents in the Treatment of Eosinophilic Esophagitis: Literature Review

S0345 Safety and Efficacy of Long-Term Treatment of EoE With Fluticasone Propionate Orally Disintegrating Tablet (APT-1011): Results From 40 Weeks Treatment in a Phase 2b Randomized Double-Blind Placebo-Controlled Trial

INTRODUCTION: APT-1011, a novel fluticasone propionate orally disintegrating tablet, induced histological remission and symptom improvement in adults with eosinophilic esophagitis (EoE) after 12 weeks in a phase 2b study. We aimed to evaluate long-term safety and efficacy of APT-1011 in maintaining remission for 52 weeks. METHODS: The FLUTE trial was a 2-part randomized, double-blind, placebo-controlled, dose-ranging study of APT-1011 vs placebo. Participants from 71 sites in 6 countries (N. America; Europe) were randomized in Part 1 to APT-1011 (1.5 mg HS or BID; 3 mg HS or BID) or placebo for 12 weeks. In Part 2, histological responders (≤6 eos/HPF) at Week 12 continued the same treatment to Week 52, and non-responders were assigned to 3 mg BID to Week 52. Histologic remission was evaluated at Weeks 26 and 52. Additional endpoints included endoscopic activity, symptoms and safety. RESULTS: Of 97 subjects who completed Part 1, 93 entered Part 2. Responder rates in Part 1 were 80% 3 mg BID; 67% 3 mg HS; 86% 1.5 mg BID; 48% 1.5 mg HS and 0% placebo. For APT-1011 responders at Week 12, daily doses of 3 mg and 6 mg resulted in sustained remission rates (64-84%) compared to 1.5 mg daily (30%) (Table 1). Of participants on placebo in Part 1, 80% had histological remission at Week 26 with 67% maintaining remission at Week 52. Of APT-1011 non-responders in Part 1, 26% achieved histological remission with ongoing treatment (3 mg BID) at Week 52 (Table 2). For APT-1011 responders in Part 1, the reduction in the number of dysphagia episodes at Week 12 was maintained or further reduced in Part 2; global EoE symptom scores continued to improve for the 3 mg BID and 3 mg HS groups; endoscopic improvement (EREFs) continued for all APT-1011 groups (Figure 1). The most common adverse events were oral/esophageal candidiasis in 11/93 (12%), the majority with BID dosing (7/11 3 mg BID; 3/11 1.5 mg BID; 1/11 3 mg HS). Two abnormal ACTH tests were reported at Week 52; one associated with 19-nortestosterone use and another with lab draw at the incorrect time. CONCLUSION: APT-1011 is highly efficacious for treatment and maintenance of histologic remission in adults with EoE over 52 weeks. The 3 mg HS dose demonstrated the best benefit/risk balance of efficacy and safety, for both induction and maintenance of remission over 52 weeks, with the added benefit of once daily dosing. In addition, one out of 4 APT-1011 treatment failures in Part 1of this study, responded to continued high dose APT-1011.Table 1.: Maintenance of Histological Response Analysis at Weeks 26 and 52 in Week 12 Responders.Table 2.: Histological Response at Week 26 and Maintenance of Response at Week 52 Analysis in Week 12 Non-responders.Figure 1.: Dysphagia Episodes, Global EoE Symptom Scores and EREF Scores over Time by APT-1011 Dosing Group.

Treatment for eosinophilic esophagitis.

To summarize current dietary and pharmacologic approaches in the treatment of eosinophilic esophagitis (EoE). Studies comparing dietary approaches in EoE treatment support empiric elimination diets as the preferred approach to dietary EoE treatment, with no data to support use of currently available allergy tests to guide specific food elimination diets. Swallowed topical corticosteroid therapy is the current standard of care in pharmacologic EoE treatment, with similar effectiveness of fluticasone and budesonide, but their discontinuation results in return of both EoE symptoms and disease. A number of nonsteroid-based therapies are currently under investigation for the treatment of EoE, which are focused on targeting disease at a cellular level. EoE can be treated with diet or medications. Empiric elimination is presently the preferred dietary approach. Swallowed steroids is the standard of care to treat EoE with medication; however, there are several promising drugs currently undergoing clinical trials.

290 COMPARATIVE EFFICACY OF CORTICOSTEROIDS FORMULATIONS FOR THE MANAGEMENT OF EOSINOPHILIC OESOPHAGITIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

Abstract Topical corticosteroids are the foundation of pharmacologic treatment for eosinophilic oesophagitis (EoE) and administered mainly as nebulized swallowed fluticasone or budesonide viscous solution (BVS). Recently, a budesonide orodispersible tablet (BOT) has been approved for the treatment of EoE. The ideal formulation of topical corticosteroid delivery is unclear. Therefore, we aimed to compare the efficacy of BOT with other topical corticosteroid formulations for achieving histological remission in adult patients with EoE in a network meta-analysis (NMA). Methods A systematic literature review was performed using Medline and EMBASE from 1990 to July 2019. Eligible studies evaluated adult patients with a diagnosis of EoE treated with a topical corticosteroid in a randomized controlled trial. The outcome of interest was the proportion of patients achieving induction of histological remission (peak esophageal eosinophil count &amp;lt;5 eosinophils/high-power field). Direct comparisons were performed using the Mantel–Haenszel method and an NMA was performed using a fixed effect Bayesian framework with Markov Chain Monte Carlo simulations. Heterogeneity between studies was analyzed using the Cochrane Q test and consistency was verified. Results The search yielded 321 references and 6 (447 patients) were included in the quantitative summary. In the NMA, all formulations of topical corticosteroids were associated with greater histological remission rates than placebo. BOT was associated with a significantly higher rate of histological remission compared to BVS (odds ratio [OR] = 4.9; 95% credible interval [CrI] = 1.4,19.1), fluticasone (OR = 7.4; 95%CrI = 1.7,34.5), nebulized swallowed budesonide (NSB) (OR = 25.0; 95%CrI = 2.9,247.2) and placebo (OR = 387.6; 95%CrI = 97.5,2275.6). Similar trends were shown in direct comparisons. Analysis of the ranking of treatment options based on probability of effectiveness found BOT to be most probable followed by BVS, fluticasone, NSB, and placebo, consecutively. Conclusion This NMA of randomized controlled trials suggests that BOT is significantly more likely to achieve histological remission in adult patients with EoE compared to BVS, fluticasone, and NSB. We hypothesize that the superiority of BOT is related to increased contact time and targeting all inflammatory sites in the oesophagus, in contrast to other formulations. This NMA suggest that BOT is the first choice therapy amongst topical corticosteroids for the management of EoE.

Comment on Casiraghi et al. "Mucoadhesive Budesonide Formulation for the Treatment of Eosinophilic Esophagitis" 2020, 12, 211.

In their article, Casiraghi, A. et al. describe a few relevant methods to assess the quality of a pharmaceutical preparation of oral viscous budesonide, intended to be swallowed, and treat the esophagus in eosinophilic esophagitis patients. They choose the following methods for this purpose: rheological properties, syringeability, mucoadhesiveness, and in vitro penetration of budesonide in porcine esophageal tissue. At the end of the article, they concluded that the best formulation of oral viscous budesonide was the one already being used in hospitals, based on xanthan gum. In their article, the authors did not emphasize that this specific formula was developed by the compounding pharmacist Eyal Zur from Israel and was published eight years before, as part of an article in the International Journal of Pharmaceutical Compounding. The purpose of this comment is to give the appropriate credit to the pharmacist who first developed and published this well designed formulation.