Dataset Information

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis.

ABSTRACT:

Objective

To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE).

Design

Adults with active EoE (n=76) randomly received 14 days' treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm(2 )hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's preference for drug formulation.

Results

Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients.

Conclusions

BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation.

Clinicaltrialsgov number

NCT02280616; EudraCT number, 2009-016692-29.

SUBMITTER: Miehlke S

PROVIDER: S-EPMC4789829 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis.

Miehlke Stephan S Hruz Petr P Vieth Michael M Bussmann Christian C von Arnim Ulrike U Bajbouj Monther M Schlag Christoph C Madisch Ahmed A Fibbe Christiane C Wittenburg Henning H Allescher Hans Dieter HD Reinshagen Max M Schubert Stefan S Tack Jan J Müller Michaela M Krummenerl Patrick P Arts Joris J Mueller Ralph R Dilger Karin K Greinwald Roland R Straumann Alex A

Gut 20150319 3

<h4>Objective</h4>To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE).<h4>Design</h4>Adults with active EoE (n=76) randomly received 14 days' treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, ...[more]

PMID: 25792708

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Project description:BackgroundAn orodispersible form of budesonide has recently been approved for the targeted treatment of eosinophilic oesophagitis in the United Kingdom, Europe, Australia, Canada and the United States, following favourable results from a randomised controlled trial. This is the first dedicated real-world study exploring the safety and efficacy of budesonide orodispersible tablets for induction therapy in the treatment of eosinophilic oesophagitis while providing insights into its management.ObjectivesThe primary objective was histologic remission, defined as less than 5 eosinophils per high-powered field. The secondary objectives included histologic response (>50% reduction in peak eosinophil count), clinical remission (complete resolution of symptoms documented on clinic letters), clinical response (improvements in symptoms as reported on clinical letters), endoscopic remission (Endoscopic Reference Score (EREFS) score = 0), and endoscopic response (improvement in EREFS score). The EREFS scores were calculated based on the severity and presence of rings, longitudinal furrows, strictures, oedema and exudates on endoscopic images. Adverse events and safety profiles were also recorded.DesignA multicentre cohort study examining the effectiveness of 1 mg, twice daily, budesonide orodispersible tablet induction therapy for the treatment of eosinophilic oesophagitis.MethodsEthics approval was obtained through the Western Australia Health: Governance, Evidence, Knowledge, Outcomes system for assessment of Audit and Quality Activities. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.ResultsA total of 43 patients (29 males, 14 females; median age 39) were recruited. Forty-one patients were included in the analysis. After induction therapy, 30 patients (73%) achieved histologic remission, and 35 patients (85%) demonstrated histologic response. Thirty-nine patients (95%) achieved clinical response, and 28 patients (68%) achieved clinical remission. An endoscopic response was seen in 37 patients (90%), and 16 patients (39%) achieved endoscopic remission. No significant adverse events were identified.ConclusionBudesonide orodispersible tablet is an effective induction therapy for eosinophilic oesophagitis, as evidenced by its high histologic remission rate and favourable safety profile.

Project description:ObjectiveThe influence of eosinophilic oesophagitis (EoE)-associated inflammation upon oesophageal epithelial biology remains poorly understood. We investigated the functional role of autophagy in oesophageal epithelial cells (keratinocytes) exposed to the inflammatory EoE milieu.DesignFunctional consequences of genetic or pharmacological autophagy inhibition were assessed in endoscopic oesophageal biopsies, human oesophageal keratinocytes, single cell-derived ex vivo murine oesophageal organoids as well as a murine model recapitulating EoE-like inflammation and basal cell hyperplasia. Gene expression, morphological and functional characterisation of autophagy and oxidative stress were performed by transmission electron microscopy, immunostaining, immunoblotting, live cell imaging and flow cytometry.ResultsEoE-relevant inflammatory conditions promoted autophagy and basal cell hyperplasia in three independent murine EoE models and oesophageal organoids. Inhibition of autophagic flux via chloroquine treatment augmented basal cell hyperplasia in these model systems. Oesophageal keratinocytes stimulated with EoE-relevant cytokines, including tumour necrosis factor-α and interleukin-13 exhibited activation of autophagic flux in a reactive oxygen species-dependent manner. Autophagy inhibition via chloroquine treatment or depletion of Beclin-1 or ATG-7, augmented oxidative stress induced by EoE-relevant stimuli in murine EoE, oesophageal organoids and human oesophageal keratinocytes. Oesophageal epithelia of paediatric EoE patients with active inflammation displayed increased autophagic vesicle content compared with normal and EoE remission subjects. Functional flow cytometric analysis revealed autophagic flux in human oesophageal biopsies.ConclusionsOur findings reveal for the first time that autophagy may function as a cytoprotective mechanism to maintain epithelial redox balance and homeostasis under EoE inflammation-associated stress, providing mechanistic insights into the role of autophagy in EoE pathogenesis.

Project description:ObjectiveAdvancing the understanding of the pathophysiology of eosinophilic oesophagitis (EoE) and other eosinophilic gastrointestinal diseases (EGIDs) has spurred research into targeted biological therapies, while the conclusive therapeutic efficacy of biologics remains uncertain. In this review, we conducted a meta-analysis of all RCTS of biologics in the treatment of EoE to evaluate their efficacy and safety and discussed their treatment of non-EoE EGIDs.MethodsWe searched the PubMed, EMBASE, Cochrane Library, and Web of Science databases. Double-blind randomized controlled trials comparing biologics with placebo in patients with EoE and non-EoE EGIDs were collected and further screened for inclusion and exclusion. The caliber of the included literature was evaluated using the Cochrane risk assessment tool findings. Data extraction and meta-analysis were conducted using RevMan 5.4 and Stata 17.0. Clinical response and histological remission were the major endpoints.ResultsOur search retrieved 3,237 articles. There were seven trials in total, comprising 792 people with EoE. Key outcomes of this meta-analysis include the following: Anti-IL-5 biologics exhibited statistically significant benefits in histological remission (RR 2.03 [CI 1.45-2.85]; p < 0.0001) compared to the placebo, but there was no significant difference in symptom relief (RR 1.06 [CI 0.88 to 1.28]; p = 0.53); anti-IL-4/13 biologics had significant effects on histologic improvement (RR 10.48 [CI 5.54-19.82]; p < 0.00001) and symptom related score reduction (RR 1.44 [CI 1.08-1.93]; p = 0.01), with a better outcome for endoscopic remission than with placebo (SMD-1.06 [CI-1.26-0.86], p < 0.00001); no statistically significant differences in adverse effects were observed between the intervention and control groups.ConclusionsOur findings suggest that the biologics currently being investigated are considered safe and effective treatments for EoE, while their efficiency varies. However, the discussion of biologics in non-pharyngitis EGID is hampered by a lack of research, necessitating more research in high-quality trials.

Dataset Information

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis.

Objective

Design

Results

Conclusions

Clinicaltrialsgov number

Publications

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis.

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