BARCELONA, Spain — An 8-week course of high-dose budesonide orodispersible tablets significantly reduced the risk for esophageal stricture after extensive endoscopic submucosal dissection (ESD), according to results from a multinational, randomized, placebo-controlled trial.

The treatment also reduced the need for subsequent endoscopic dilation. "Among patients who did require dilation, the mean number of dilations was also lower with high-dose budesonide," said Annemijn D.I. Maan, MD, a PhD candidate in the Department of Gastroenterology and Hepatology at Erasmus MC Cancer Institute, Rotterdam, Netherlands. 

Maan presented the late-breaking findings here at United European Gastroenterology (UEG) Week 2026. 

Strictures a Major Complication of Extensive ESD

Endoscopic techniques, including ESD, are increasingly used instead of surgery to treat early esophageal cancers. However, a major drawback of ESD is the risk for subsequent esophageal strictures.

The risk can reach 70%-90% when the resulting mucosal defect involves more than three quarters of the esophageal circumference, Maan explained. Corticosteroids are already used in clinical practice to prevent strictures, but evidence from adequately powered randomized trials has been limited.

PEGASUS-1 was a multinational, double-blind trial that initially randomized patients to high-dose budesonide orodispersible tablets (2 mg twice daily), low-dose budesonide (1 mg twice daily), or placebo, starting the day after ESD and continuing for 8 weeks. The low-dose arm was subsequently closed following a prespecified interim analysis.

Eligible patients had substantial mucosal defects after ESD: at least 50% of the esophageal circumference for squamous cell carcinoma, and at least 75% for Barrett esophagus-associated high-grade dysplasia or early adenocarcinoma. Patients receiving other corticosteroids or chemotherapy for esophageal cancer were excluded.

A total of 119 patients were randomized. The modified full analysis set of 102 patients included 51 patients receiving high-dose budesonide, 18 receiving low-dose budesonide, and 33 receiving placebo.

The primary endpoint was absence of esophageal stricture at week 8, with stricture defined as the need for dilation and/or inability to pass a standard endoscope.

Benefit Varied With Extent of Mucosal Defect

At week 8, 66.7% of patients receiving budesonide 2 mg twice daily remained free of esophageal strictures compared with 42.4% of those receiving placebo (P = .0098). With budesonide 1 mg twice daily, 55.6% were stricture-free.

The treatment also reduced the need for subsequent endoscopic dilation. Dilation was required in 25.5% of patients receiving high-dose budesonide compared with 48.5% receiving placebo. Among patients who did require dilation, the mean number of procedures was 2.8 and 4.3, respectively. 

The benefit of budesonide was particularly marked among patients with extensive, but not quite circumferential, mucosal defects. Among patients with defects involving 75% to less than 95% of the esophageal circumference, 92% receiving high-dose budesonide remained stricture-free compared with 59% receiving placebo.

However, outcomes remained poor among those at the highest risk. When the defect involved 95% or more of the circumference, only 26% of patients receiving high-dose budesonide remained stricture-free, although none of those receiving placebo did so. 

Results were broadly consistent across tumor types. Stricture-free rates with high-dose budesonide vs placebo were 77.3% compared with 53.8% among patients with squamous cell carcinoma, and 58.6% vs 35.0% among those with Barrett esophagus-associated high-grade dysplasia or early adenocarcinoma. 

Swallowing outcomes also favored budesonide numerically: 82.4% of patients receiving high-dose budesonide had an Ogilvie dysphagia score of 1 or less at week 8 compared with 66.7% receiving placebo, indicating an ability to eat a normal diet or at least some solid foods. 

Candidiasis More Common With Budesonide

The principal drug-related safety signal was candidiasis. Oral, oropharyngeal, or esophageal candidiasis occurred in 29.1% of patients receiving high-dose budesonide compared with 2.5% receiving placebo. All cases resolved and/or were successfully treated with antifungal therapy, according to the investigators. 

Maan noted that the 2-mg twice-daily dose used for stricture prevention was higher than the dose used to treat eosinophilic esophagitis. 

Need to Compare With Systemic Corticosteroids

"It doesn't solve the problem for all patients, especially the highest-risk patients, but it improves their outcomes," Alanna Ebigbo, MD, professor and director of gastroenterology and endoscopy at St. Josef-Hospital, Ruhr University Bochum, Germany, and a co-moderator of the session, told Medscape Medical News. 

"If budesonide helps, at least in the medium-risk patients, then it's a good starting point," he added. 

However, the findings leave a need for better preventive strategies for patients at the highest risk, particularly those with near-circumferential mucosal defects, Ebigbo said.

In addition, he cautioned, "the study was not compared with our standard of care, which is systemic steroids."

During the audience discussion, one delegate questioned why systemic oral corticosteroids had not been included as an active comparator, given their use in clinical practice. Maan agreed that a head-to-head comparison would be an important next step.

A potential advantage of budesonide orodispersible tablets is the prospect of fewer systemic adverse effects, said Ebigbo. Although systemic corticosteroids can also be taken orally, they carry substantially more systemic complications, including diabetes and an increased risk for infections.

Similarly, Maan described budesonide as "the little brother of prednisone," noting its extensive first-pass metabolism.

Maan reported no conflicts of interest. Ebigbo reported no relevant conflicts of interest. PEGASUS-1 was sponsored by Dr. Falk Pharma GmbH, and two study coauthors were employees of the company.