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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 budeso...
Contexts in source publication
Context 1
... treatment groups had similar baseline characteristics (Table 1), being typical for an adult patient population with EoE. Both study arms had a similar peak eosinophil count and moderate to severe esophageal symptom scores as assessed by NRS for dysphagia, odynophagia; NRS for PatGA and PGA, EEsAI-PRO, and dysphagia-free days. ...Context 2
... study arms had a similar peak eosinophil count and moderate to severe esophageal symptom scores as assessed by NRS for dysphagia, odynophagia; NRS for PatGA and PGA, EEsAI-PRO, and dysphagia-free days. HRQoL, as measured by modified SHS and EoE-QoL-A scores, was moderately impaired in both treatment groups at baseline (Table 1). ...Context 3
... (41) 10 (35) bid, twice daily; CI, confidence interval; n, valid number; PPI, proton pump inhibitor. a Previously reported efficacy of drug interventions in the patient's history is presented in Supplementary Table 11. Figure 1. ...Similar publications
Background:
APT-1011, a fluticasone propionate orally disintegrating tablet formulation, is under investigation for the treatment of eosinophilic oesophagitis (EoE).
Aims:
To evaluate the safety and tolerability of APT-1011 administered to patients with EoE and to assess the effect on clinical symptoms of EoE, endoscopic appearance and oesophage...
Citations
... In adults, data from randomised placebo-controlled trials show that in a dosage of 1 mg two times per day, orodispersible budesonide achieved remission after 12 weeks in 85% of patients. 12 Viscous budesonide formulations using sucralose or other substrates (evaluated in a prospective randomised placebo-controlled trial only) may be equally, less or more effective. ...
Objective
To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.
Methods
A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical ‘how to prepare and use’ OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly.
Results
2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed.
Conclusion
A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.
... JORVEZA has been evaluated in multiple placebo-controlled trials and found out to be effective in inducing clinical and histological response when administered at an induction dose of 1 mg twice daily for 12 weeks [21]. Followed by an extension trial of 204 patients with EoE, a maintenance dose of 1 mg per day was administered also proved its effectiveness for 48 weeks in 75% of the subjects [22]. ...
Purpose: Data on Eosinophilic esophagitis in Israel is sparse. We appraised the clinical, endoscopic, and histological characteristics of 50 Israeli adults with EoE. Methods: Medical records of 50 adult patients with established diagnoses of EoE who were referred to our center from 2020 until 2023 at Bnai Zion Medical Center, Haifa, Israel, were reviewed. Results: Fifty patients with EoE were included, the mean age at diagnosis was 34±9.5 years. The sex ratio of males to females was approximately 2:1 with 34 males (68%) and 16 females (32%). Twenty-two of the 50 patients had a history of allergic diseases, Symptoms at diagnosis were as follows: Dysphagia was the primary presenting symptom observed (n=25, 50%), followed by food impaction (n=17, 34%) and GERD-like symptoms (n=14, 28%). Less frequent symptoms included vomiting, nausea, and chest pain. The most common endoscopic findings were normal mucosa (n=21, 42%) followed by Trachealization (n=17, 34%), esophagitis (n=7, 14%), and exudates (n=5, 10%). 66% of the subjects were initially treated with proton-pump inhibitors (PPIs). Nine patients (18%) were asymptomatic without any treatment. The remaining eight patients (16%) were given topical steroids. Clinical and histological resolution was detected in 50% of the patients who underwent a second EGD after 6–8 weeks of PPI. Conclusion: Our current study depicts the clinical features of adult patients with EoE in north Israel. This is the first demographic study in Israel that defines the clinical, endoscopic, and histological manifestations of EoE in the adult population.
... Several pharmacological treatment regimens were found in the literature, including oral budesonide formulations, calcineurin inhibitors, mycophenolate mofetil, PDE-4 inhibitors, as well as systemic corticosteroids [6][7][8][9][10]. As topical corticosteroids are the first line of oral LP, we opted for Jorveza™, a novel budesonide orodispersible tablet (BOT) designed for EoE highly selective to the oesophagus [11]. Prior to the introduction of BOT, EoE treatment was largely based on topical steroid therapies. ...
... Surprisingly, she also reported marked improvement in her oral LP, with near-complete healing of ulcerations. A follow-up EGD was performed 2 months post-therapy initiation, which was normal apart from incidental candidiasis (a common side effect of BOT [11]), after which the patient received fluconazole 200 mg BD for 14 days. Biopsies taken from the length of the oesophagus showed no evidence of existing oesophagitis, with an entirely normal mucosal appearanceapart from diffuse candida hyphae and spores without inflammatory response in the distal oesophagus (Fig. 3). ...
... In our patient, there was total endoscopic and symptomatic resolution of ELP, and also of her oral lesions. This was achieved using BOT, which is usually administered by the patient placing the tablet on the tongue and pressing it on the top of the hard palate for it to slowly disintegrate, thereby causing effervescence and hypersalivation and a steady "stream" of saliva loaded with BOT to go through the mouth, oropharynx, and oesophagus [11]. When analysing how this drug is administered, it is easy to understand that the potential local effect of the drug has also aided in the quick resolution of the patient's oral lesions, being a serendipitous effect. ...
Introduction
Lichen planus is a relatively common inflammatory condition of the nails, skin, and mucosal surfaces. Oesophageal involvement of lichen planus is thought to be very rare, mainly described in case reports, but is associated with a high risk of oesophageal stenosis as well as squamous cell carcinoma. No evidence-based treatment recommendations exist, with the majority of described treatment regimens involving systemic immunosuppression.
Case Report
In this case report, we describe a novel approach in treating oesophageal lichen planus in a patient with budesonide orodispersible tablets, a treatment normally reserved for eosinophilic oesophagitis. The patient achieved complete relief of dysphagia, with a follow-up oesophagogastroduodenoscopy 2 months after treatment commencement being macroscopically and microscopically free of inflammatory activity. This case report is to our knowledge the first to report this treatment regimen in oesophageal lichen planus.
Conclusion
We consider a trial of budesonide orodispersible tablets a reasonable initial management as it’s a local therapy specific to the oesophagus with a more benign side effect profile than systemic immunosuppression, but further studies need to be undertaken to corroborate our findings. Also, based on the severity and malignant potential of oesophageal lichen planus, we suggest that physicians be liberal in ordering oesophagogastroduodenoscopy with biopsy taking as part of the workup of dysphagia in a patient with known lichen planus.
... Les corticostéroïdes topiques sont offerts sous forme de nébuliseur de propionate de fluticasone pour prise orale ou sous forme topique orale (budésonide en solution visqueuse ou budésonide en comprimés orodispersibles) (tableau 1). La seule préparation approuvée au Ca nada pour les adultes (et non les enfants) atteints d'oesophagite à éosinophiles est le budésonide en comprimés orodispersibles 39,40 . Un essai randomisé contrôlé sur le budésonide (comprimé orodispersible, 1 mg par voie orale 2 fois par jour) a fait état d'une amélioration histologique, endoscopique et symptomatologique dès la 6 e semaine chez 58 % des malades, contre 0 % avec le placebo 39 . ...
... La seule préparation approuvée au Ca nada pour les adultes (et non les enfants) atteints d'oesophagite à éosinophiles est le budésonide en comprimés orodispersibles 39,40 . Un essai randomisé contrôlé sur le budésonide (comprimé orodispersible, 1 mg par voie orale 2 fois par jour) a fait état d'une amélioration histologique, endoscopique et symptomatologique dès la 6 e semaine chez 58 % des malades, contre 0 % avec le placebo 39 . Une rémission soutenue (48 semaines) a été observée avec le budésonide (comprimé orodispersible, 0,5 mg ou 1 mg 2 fois par jour) chez 73,5 % des personnes qui recevaient la dose de 0,5 mg et 75 % des personnes qui recevaient la dose de 1 mg, contre 4 % des personnes sous placebo 40 . ...
... Wyniki pracy opublikowanej w 2020 roku wskazują na wystąpienie remisji histologicznej u 64,9% pacjentów poddanych terapii miejscowymi GKS, w porównaniu do 13,3% osób otrzymujących placebo [19,20]. W innym randomizowanym badaniu klinicznym uzyskano remisję zarówno histologiczną, jak i kliniczną u 57,6% pacjentów po 6 tygodniach terapii i u 84,7% chorych po 12 tygodniach terapii budezonidem w postaci tabletki rozpuszczającej się w jamie ustnej [20,21]. Sugeruje się więc, że terapia GKS powinna trwać przynajmniej 12 tygodni [20]. ...
... 23 Use of the budesonide slurry has now been replaced by an orally disintegrating tablet formulation. 24 The formulation is mucoadhesive, which allows budesonide to adhere to the oesophageal mucosa providing prolonged local release of drug and reduced systemic absorption, which minimises adverse effects. 25 In clinical trials, the reported clinical and histological remission rate for orodispersible budesonide was 85% after 12 weeks; 24 however, longer-term data have shown a clinical and histological remission rate of 75%. ...
... In clinical trials, the frequency was not dose related and the cases were of mild to moderate severity. 24,26 Patients can be treated with topical or systemic antifungal therapy, as appropriate, while continuing treatment with orodispersible budesonide. ...
Eosinophilic oesophagitis is a chronic inflammatory disease related to food allergy that should be suspected in patients presenting with food bolus impaction, or a history of dysphagia with or without atopy. The 6 most common food triggers are animal milk proteins, wheat, eggs, soy, nuts and seafood.
Eosinophilic oesophagitis is a histological diagnosis with at least 15 eosinophils (60 eosinophils per mm2) per high-power field on oesophageal biopsy. Alternative causes of oesophageal eosinophilia should be excluded.
Patients with eosinophilic oesophagitis require lifelong management. Depending on patient preference, this may involve dietary exclusion of confirmed food trigger(s) or pharmacological treatment. The mainstays of pharmacological treatment are swallowed topical corticosteroids and proton pump inhibitors, but several monoclonal antibodies are currently under investigation for treatment of eosinophilic oesophagitis.
... Long-term follow-up has revealed EoE's potential to progress to a fibrostenotic phenotype with development of esophageal strictures (3,4). Swallowed topical corticosteroids are the most widely used therapeutic modality with proven efficacy in both short-and long-term management (5,6). In addition, the anti-IL4/IL13 antibody dupilumab has been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) (7). ...
BACKGROUND
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 six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastro-esophageal 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%; non-specific esophagitis 33.3% ). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (IQR 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, 62.2% year 6). Sequential RNA sequencing analyses revealed only seven genes associated with this progression (with TSG6 and ALOX15 among the top three upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6, 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).
Conclusion
Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes appear 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.
... The only formulation approved in Canada for adults (not children) with eosinophilic esophagitis is budesonide in an orodispersible tablet. 39,40 A randomized controlled trial of budesonide (orodispersible tablet, 1 mg orally, twice daily) showed histologic, endoscopic and symptom improvement as early as 6 weeks in 58% of patients, compared with 0% of patients who received placebo. 39 Sustained remission (48 wk) with budesonide (orodispersible tablet, 0.5 mg or 1 mg, twice daily) was seen in 73.5% who received the 0.5 mg dose and 75% of patients who received the 1 mg dose, compared with 4% of patients who received placebo. ...
... 39,40 A randomized controlled trial of budesonide (orodispersible tablet, 1 mg orally, twice daily) showed histologic, endoscopic and symptom improvement as early as 6 weeks in 58% of patients, compared with 0% of patients who received placebo. 39 Sustained remission (48 wk) with budesonide (orodispersible tablet, 0.5 mg or 1 mg, twice daily) was seen in 73.5% who received the 0.5 mg dose and 75% of patients who received the 1 mg dose, compared with 4% of patients who received placebo. 40 Median time to relapse was 87 days in the placebo group, compared with 350 days in the treated groups. ...
... The second group was composed of 14 consecutive patients suffering from active EoE who participated in a trial [14] and received active treatment with orodispersible budesonide tablets at a dose of 1 mg twice daily for 6 weeks. EoE diagnoses were based on the criteria proposed by Liacouras et al. [15]: symptoms of esophageal dysfunction and infiltration of ≥15 eosinophils in at least 1 high-magnification field (400×) derived by at least 6 esophageal biopsies and no clinico-histological response to proton pump inhibitor therapy. ...
Endoluminal functional lumen impedance planimetry (EndoFLIPTM) has become the gold standard to evaluate esophageal distensibility, although the study itself and its analysis present challenges. We propose here a new method to assess lower esophageal distension capacity that overcomes several limitations of prior approaches, including incomplete and corrupted EndoFLIPTM recordings. Esophageal distension capacity was evaluated with a 16-channel EndoFLIPTM in 10 controls and 14 patients with eosinophilic esophagitis (EoE). Controls were evaluated once. EoE patients were evaluated at baseline and after at least six weeks of treatment with orodispersible budesonide tablets, 1 mg bd. Balloon volumes were increased by 5 mL stepwise, either reaching a maximum volume of 60 mL or a maximum balloon pressure of 60 mmHg. Recordings were analyzed with a homemade R script. The mean esophageal diameter at 60 mL, D (60 mL), was calculated or extrapolated depending on whether the 60 mL volume was reached. By fitting a Michaelis–Menten curve across all measured diameters throughout all constant volume steps, the mean D (60 mL) was estimated. For control subjects, the mean ± SD value of D (60 mL) was 17.08 ± 1.69 mm, and for EoE patients at baseline, D (60 mL) was 14.51 ± 2.68 mm. After six weeks of treatment of EoE patients, D (60 mL) significantly increased to 16.22 ± 1.86 mm (paired Wilcoxon signed test: p = 0.0052), although the values for control subjects were not reached. The estimated mean esophageal diameter at 60 mL is a good proxy for esophageal distension capacity, which correlates with clinical outcomes in EoE. The method presented in this study overcomes difficulties encountered during the standard measurement protocol, allowing the analysis of recordings from incomplete and corrupted registries.
... Significant advances in the treatment of EoE have made the correct diagnosis of patients with dysphagia increasingly valuable. Budesonide orodispersible tablets (BOT)-a licensed and NICE-approved therapy for adults with EoE-achieved histological remission in over 90% of patients, and symptom relief in 85%, within 12 weeks of starting treatment.8 Being able to eat normally without dietary restrictions helps to reduce the social and emotional toll of EoE. ...
LINKED CONTENT
This article is linked to Kiran et al papers. To view these articles, visit https://doi.org/10.1111/apt.17781 and https://doi.org/10.1111/apt.17811
