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In patients with eosinophilic esophagitis (EoE), a special formulation of the corticosteroid budesonide was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks, researchers reported.

Over 12 weeks, more patients given the viscous, immediate-release topical steroid than placebo recipients achieved the primary endpoint of a stringent histologic response of ≤6 eosinophils/high power field: 53.1% versus 1.0% (52% change from baseline, 95% CI 43.3%-59.1%, P<0.001), according to Ikuo Hirano, MD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues.

In addition, as shown in the study online in , more treated patients also achieved a symptom response: 52.6% versus 39.1% (13% change, 95% CI 1.6%-24.3%, P=0.024).

Budesonide oral suspension (BOS) was also well tolerated, and most adverse events were mild to moderate in severity, the researchers noted.

The double-blind phase III trial, conducted at 66 centers in the U.S. from 2015 to 2019, evaluated the efficacy and safety of BOS in patients ages 11 to 55 with EoE-related dysphagia. The mean age of patients in both arms was just under 34, and about 60% in both arms were male. More than 90% in both groups were white, and body mass index was elevated in each, at 27.5 and 28.2, respectively.

Overall, 318 patients were randomized (213 to BOS and 105 to placebo), and received at least one dose of study treatment.

In other outcomes, BOS-treated patients also showed greater improvement (minimum 30% reduction) in least-squares mean scores on the dysphagia symptom questionnaire (DSQ), and EoE endoscopic reference score (EREFS) over 12 weeks, with the following reductions from baseline:

• DSQ -13.0 (1.2) versus -9.1 (standard error 1.5), change -3.9 (95% CI -7.1 to -0.8, P=0.015)

• EREFS -4.0 (0.3) versus -2.2 (standard error 0.4) (change -1.8, 95% CI -2.6 to -1.1, P<0.001)

Only 30% of patients achieved a full response, however, highlighting the difficulty of meeting both histologic and symptom endpoints even in a clinical trial setting, the researchers said.

"This study addresses the existing unmet medical need of patients with EoE in the United States," Hirano and associates wrote, calling the study the largest clinical trial to date of a pharmacologic therapy for EoE employing modern trial design elements.

Topical corticosteroids, proton-pump inhibitors (PPIs), and elimination diets are all recommended for management of EoE in the American College of Gastroenterology's , but there are no FDA-approved pharmacologic therapies for EoE, although topical corticosteroid formulations designed for asthma are often used off-label.

"These are not formulated for esophageal delivery and thus are neither standardized nor optimized for EoE," the researchers wrote. "Inadequate treatment due to suboptimal drug delivery may fail to control inflammation, which can be associated with an increased risk of food impaction, as well as increased utilization of and decreased responsiveness to esophageal dilation."

Hirano described BOS as a unique liquid formulation developed specifically for esophageal delivery, which may ease difficulties commonly encountered in obtaining insurance coverage for off-label medications.

"The study supports current clinical guideline recommendations regarding the use of swallowed topical corticosteroids for EoE as well as ongoing development of BOS," he told MedPage Today.

The team's study is the first phase III clinical trial for EoE completed in the U.S., he noted. "It is also the first study ever conducted using a validated patient-reported outcome instrument as a co-primary endpoint and using validated secondary endpoints for endoscopic and histologic activity."

Asked for his perspective, Salmaan A. Jawaid, MD, of Baylor College of Medicine in Houston, who was not involved with the study, noted that FDA approval of this budesonide formulation is pending.

At Baylor, he said, "we have significant difficulty in getting budesonide suspension as it requires formulation by a special pharmacy. If approved by the FDA, budesonide oral suspension will be the first FDA-approved medication specifically directed at treating EoE. Approval will enhance access to budesonide oral suspension, thereby promoting widespread usage."

Previous research from Europe found that an orodispersible budesonide tablet delivered directly to the esophagus induced complete remission in patients with PPI-refractory EoE.

Hirano said that one limitation of his team's study is that it may have enrolled a proportion of patients with more severe disease compared with the European study owing to more stringent inclusion criteria -- i.e., more patients with a history of esophageal stricture and patients who did not respond to initial PPI therapy as per consensus guidelines in effect at the time of the study.

An additional limitation, the researchers said, was the exclusion of certain patients with severe esophageal strictures defined by the inability to traverse the esophagus with a standard adult upper endoscope. Furthermore, whether individuals with milder presentations would respond similarly to BOS is unknown, although the results of prior studies have suggested comparable or even greater treatment effects in patients with less severe EoE, the team noted.

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