Children, teens with EoE respond to budesonide oral suspension

Budesonide oral suspension is well tolerated and superior to placebo at inducing remission in paediatric patients with eosinophilic esophagitis (EoE), with the high-dose formulation offering the best results, according to the results of the phase II/III PEDEOS-1 trial.

After 12 weeks of treatment, the proportion of patients who achieved the composite primary endpoint of histological remission (peak counts of <16 eosinophils/mm²) and clinical response (≥30-percent decrease in the total score on Pediatric EoE Symptom Severity Module [PEESS v2.0]) was significantly greater in the high- and low-dose budesonide arms than in the placebo arm (69.2 percent and 46.2 percent vs 0 percent; both p<0.0001), reported senior investigator Dr Jorge Amil Dias of Centro Hospitalar Universitário São João in Porto, Portugal. [Lucendo A, et al, ESPGHAN 2024]

Results were consistent in the subgroups of children (age 2–11 years: 66.7 percent and 41.7 percent vs 0 percent) and adolescents (age 12–17 years: 7.4 percent and 50.0 percent vs 0 percent) and confirmed in the per-protocol analysis (72.2 percent and 40.9 percent vs 0 percent; p<0.0001 and p=0.0011, respectively).

“Overall, budesonide in the form of an oral suspension was well tolerated,” Amil Dias said. “There were no safety concerns identified, and the nature and frequency of adverse events (AEs) were consistent with the known safety profile of topical budesonide.”

The rates of treatment-emergent AEs were 84.6 percent in the high-dose arm, 73.1 percent in the low-dose arm, and 83.3 percent in the placebo arm. Esophageal candidiasis occurred in one patient in the high-dose arm (3.8 percent), while decreased morning serum cortisol levels were documented in one patient in the high-dose arm and another in the placebo arm. 

“No bolus impaction occurred in any patients,” Amil Dias noted.

High-dose formulation most efficacious

A total of 76 children (n=35) and adolescents (n=41) with EoE participated in PEDEOS-1. These patients were randomly assigned to receive high-dose budesonide (0.5 mg for children and 1 mg for teens, administered twice daily; n=26), low-dose budesonide (same doses but administered only once daily; n=26), or placebo (n=24) for 12 weeks. Patients could go into a 12-week open-label induction phase in the event of a bolus impaction or nonresponse at week 8. This was followed by a 24-week open-label maintenance phase.

Analyses of secondary endpoints strongly supported the efficacy of budesonide oral suspension, Amil Dias said.

Significant advantages were seen in both the high- and low-dose arms versus the placebo arm for histological remission (88.5 percent and 61.5 percent vs 0 percent), changes in eosinophil count (–228.7 and –170.2 vs –7.8 eosinophils/mm²), histological healing (peak of 0 eosinophil/mm²: 84.6 percent and 53.8 percent vs 0 percent), changes in the EoE histologic scoring system (grade score: –0.41 and –0.27 vs –0.06; stage score: –0.38 and –0.28 vs –0.05), changes in inflammation (–2.0 and –1.9 vs 0.2) and fibrosis (–0.2 and –0.3 vs 0.2) on the EoE Endoscopic Reference Score, and the rate of patients with grade 0 for all major and minor modified EREFS features (53.8 percent and 34.6 percent vs 0 percent).

“High-dose budesonide oral suspension led to clinically better results [for both histologic and endoscopic outcomes] compared with the low dose,” Amil Dias noted.

For patient-reported outcomes, similar overall clinical symptom response rates were seen across the treatment arms, although high- and low-dose budesonide showed a signal of benefit for dysphagia, he added.

Taken together, the findings from PEDEOS-1 indicate that “budesonide oral suspension at high dose is a safe and most efficacious dose for induction of remission in paediatric EoE patients,” Amil Dias concluded.