麻豆传媒

Orodispersible budesonide delivered specifically to the esophagus as a tablet was effective in inducing clinical and histological remission in patients with eosinophilic esophagitis (EoE), according to a European randomized, controlled trial.

At 6 weeks of treatment, the new topical-acting formulation of the corticosteroid (Jorveza) induced complete clinical/histological remission in about 58% of treated patients, while no placebo patient achieved remission (P<0.001), reported Alfredo J. Lucendo, MD, PhD, of Tomelloso General Hospital in Tomelloso, Spain, and colleagues.

Histologic remission, the study' secondary endpoint, was achieved by 93.6% of treated versus no placebo patients (P<0.0001). After 12 weeks, 85% of treated patients had achieved clinico-histological remission, they wrote in .

Both 6- and 12-weeks of treatment with the tablet were safe and well tolerated, but 5% of treated patients developed symptomatic mild candida, the authors noted.

The incidence of EoE, a food-related immune-mediated condition, has dramatically increased in incidence and prevalence over the past 2 decades, especially in . EoE is now the most common cause of dysphagia and bolus impaction and second only to gastroesophageal reflux disease as a cause of chronic esophagitis, according to Lucendo's group.

Budesonide targets eosinophilic inflammatory infiltrate by preventing antigen-stimulated secretion of proinflammatory signal molecules into the esophageal epithelium. The drug is dissolved against the hard palate and slowly swallowed, and is approved by the for the treatment of EoE in adults.

The study recruited 88 adults with active EoE refractory to standard doses of various proton pump inhibitors (PPIs) and randomly assigned them to budesonide 1 mg twice daily (n=59) or placebo (n=29) for 6 weeks. The mean age in both arms was 37, and 81% and 86%, respectively, were male.

Complete remission was based on both clinical and histological factors, including dysphagia and odynophagia severity ≤2 on a scale of 0 to 10 on each of the 7 days before the end of an initial 6-week double-blind phase and a peak eosinophil count <5 eosinophils per high power field. Patients not achieving complete remission at 6 weeks were then offered 6 weeks of open-label treatment.

Overall, more patients (93.6%) achieved histological remission than clinical remission. "The data underscore the repeatedly documented imperfect relationship between esophageal symptoms and the biological activity of EoE," the authors wrote, adding that this discrepancy could be due to the presence of mild esophageal strictures, which affected 15% in both study arms.

"These findings are very relevant for practice since a pill form of budesonide will improve compliance and quality of life. It makes it easier for the consumer," commented Tiffany J. Patton, MD, of the University of Chicago, to 麻豆传媒. Current options for EoE are off-label, and include mixing liquid asthma corticosteroids into a paste with a thickener, such as honey, to ensure adherence to the esophageal lining when sipped and swallowing rather than inhaling puffed asthma medications.

"It would be a good idea to compare these three modalities in trials to see which works bests," said Patton, who was not involved in the study. She added that young children may still need the sweetened paste option.

Study limitations included a design that identified neither the timing of budesonide's maximal effect as induction nor a minimal effective dose regimen. The study also excluded patients with severe strictures impassable to a standard gastroscope, whereas some strictures with a predominant inflammatory component may have responded to treatment.

Furthermore, symptomatic improvement during the unblinded open-label phase could have led to overestimation of the drug's therapeutic effect. Lastly, although concomitant treatment with PPIs continued in fewer than 12% of patients, this could have contributed to symptomatic improvement at the end of treatment.

The authors noted that "an ongoing trial with the same formulation will provide evidence on its efficacy to maintain this remission in the long term."

Comment