Eosinophilic oesophagitis (EoE) is a chronic inflammatory disease requiring long-term therapeutic management [1-3]. Currently, swallowed topical corticosteroids (STC) are the first-line medical therapy for active disease . Nonetheless, oesophageal targeting and efficacy of STC are suboptimal. A new formulation of budesonide orodispersible tablet (BOT) showed efficacy in EoE in a 6-week phase 3 trial . The current phase 3, randomised, double-blind, placebo-controlled trial evaluated the long-term efficacy and safety of the new BOT formulation for the maintenance of remission in adult patients with EoE .
Mean age was 36 years, 82.8% were male, and all patients were white. After reaching clinicohistologic remission after treatment with BOT 1.0 mg BID for 6-12 weeks, included patients (n=204) were randomised 1:1:1 in 3 groups (BOT 0.5 mg twice daily [BID], BOT 1.0 mg BID, or placebo BID).
The primary outcome –remission at week 48– was achieved in 50/68 patients in the BOT 0.5 mg BID (73.5%; P<0.001), 51/68 in the BOT 1.0 mg BID (75.0%; P<0.001), and 3/68 in the placebo groups (4.4%; see Figure). All secondary efficacy outcomes proved superiority of BOT 0.5 mg and 1.0 mg BID over placebo: a histologic relapse was experienced by 9/68 (13.2%; P<0.001), 7/68 (10.3%; P <0.001), and 61/68 (89.7%) in the BOT 0.5 mg BID, BOT 1.0 mg BID, and placebo groups, respectively. Clinical relapses occurred in 7/68 (10.3%, P<0.001), 5/68 (7.4%; P<0.001), and 41/68 (60.3%) in the 3 treatment groups. A post-hoc analysis of clinicohistologic remission revealed results in line with the primary endpoint: 48/68 (70.6%) in the BOT 0.5 mg BID (P<0.001), 50/68 (73.5%) in the BOT 1.0 mg BID (P<0.001), and 1/68 (1.5%) in the placebo groups. During the study period, no significant differences in endoscopic remission rates were found for BOT 0.5 mg and 1.0 mg BID, but a significant decrease was found with placebo (P<0.001). No differences in remission rates were found between the 2 dosages.
No serious drug-related adverse events (AEs) were reported. Most AEs were unrelated to the study drug and the most commonly reported AE was mild-to-moderate local candidiasis. In 4 patients receiving BOT, a decrease in serum morning cortisol below the lower limit of normal (6.2 μg/dL) was observed, but without symptoms of adrenal insufficiency.
In conclusion, the trial data demonstrates that BOT 0.5 mg and 1.0 mg BID were well tolerated, efficient, and safe as maintenance therapy for adult patients with EoE.
Straumann A, Lucendo AJ, Miehlke S, Vieth M, Schlag C, Biedermann L, Vaquero CS, Ciriza de Los Rios C, Schmoecker C, Madisch A, Hruz P, Hayat J, von Arnim U, Bredenoord AJ, Schubert S, Mueller R, Greinwald R, Schoepfer A, Attwood S; International EOS-2 Study Group. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology. 2020 Nov;159(5):1672-1685.e5. doi: 10.1053/j.gastro.2020.07.039. Epub 2020 Jul 25. PMID: 32721437.
- Straumann A, et al. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology 2020; 159:1672-85.
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- Lucendo AJ, Molina-Infante J, Arias A, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J 2017;5:335–58.
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