Budesonide oral suspension makes the grade in eosinophilic esophagitis

The novel formulation of budesonide for eosinophilic esophagitis (EoE) appears well tolerated and outdoes placebo in terms of histologic, symptomatic, and endoscopic outcomes over 3 months, as shown in the results of a phase III study.

“Budesonide oral suspension (BOS) is an immediate-release topical corticosteroid optimized as a viscous suspension and designed specifically for patients with EoE,” according to the investigators.

Given the lack of pharmacologic therapies approved for EoE, the encouraging findings for BOS will be a boon to patients, who “often resort to using off-label corticosteroids formulated for asthma leading to suboptimal oesophageal delivery and [problems] with medical insurance coverage owing to the off-label utilization,” they added. [Gastroenterology 2012;143:321-324; Clin Gastroenterol Hepatol 2017;15:1173-1183]

In the trial, 318 children (12.9 percent) and adults (87.1 percent) with EoE and dysphagia were randomized to receive BOS 2.0 mg twice daily (n=213) or placebo (n=105) for 12 weeks. Patient characteristics were similar between the treatment arms, with 41.8 percent of the total population having a prior oesophageal dilation.

Over 12 weeks, significantly more patients who received BOS vs placebo achieved the coprimary endpoints of stringent histologic response (≤6 eosinophils/high-power field; 53.1 percent vs 1.0 percent; p<0.001) and dysphagia symptom response (≥30 percent reduction in Dysphagia Symptom Questionnaire [DSQ] score; 52.6 percent vs 39.1 percent; p=0.024). [Clin Gastroenterol Hepatol 2021;doi:10.1016/j.cgh.2021.04.022]

BOS also produced greater improvements in least-squares mean DSQ scores (–13.0 vs –9.1; difference, –3.9, 95 percent confidence interval [CI], –7.1 to –0.8; p=0.015) and EoE Endoscopic Reference Score (EREFS; –4.0 vs –2.2; difference, –1.8, 95 percent CI, –2.6 to –1.1; p<0.001).

BOS was well tolerated, with the incidence of treatment-emergent adverse events (TEAEs) similar to that seen with placebo (61.0 percent for both). The most common TEAEs in the BOS arm were nasopharyngitis (5.2 percent), sinusitis (4.2 percent), oesophageal candidiasis (3.8 percent), oral candidiasis (3.8 percent), nausea (2.8 percent), abnormal adrenocorticotropic hormone stimulation test (2.8 percent), and cough (2.8 percent). All candidiasis-related events were mild or moderate in severity.

Serious TEAEs were rare, occurring in two patients (acute gastroenteritis with sepsis and intra-abdominal fluid collection) on BOS and one (ovarian cyst) on placebo. All events were considered unrelated to study treatment. TEAEs led to treatment discontinuation in four patients overall, and there were no life-threatening TEAEs or deaths documented.

“To date, this is the largest clinical trial of a pharmacologic therapy for EoE employing modern trial design elements, including daily electronic symptom diaries, a placebo lead-in period, and validated outcome metrics,” according to the investigators.

“Only one other phase III pharmacologic study has been published for EoE to date, assessing budesonide orodispersible tablets (BOT), in a multicentre European trial,” they said. “Rates of histologic, symptomatic, and endoscopic response were ostensibly lower in this trial of BOS than in the trial of BOT. However, the degree of heterogeneity between the two phase III trials makes it difficult to compare outcomes.” [Gastroenterology 2019;157:74-86]

The investigators believe that the present study will address the existing unmet medical need of patients with EoE in the US. Given the inclusion of patients with more severe disease, it is unknown whether those with milder presentations would respond similarly to BOS, “although the results of prior studies suggest comparable or even greater treatment effects in patients with less severe EoE.” [Gastrointest Endosc 2020;92:44-53; Gastrointest Endosc 2016;83:1142-1148]