Introduction
Budesonide orodispersible tablets (BOT) effectively induce and maintain clinical and histological remission in patients with eosinophilic esophagitis (EoE) (1, 2). A substantial fraction of patients recruited for the BUL-1 and BUL-2 studies had previously been treated with swallowed topical corticosteroids (STC) other than BOT. This post-hoc analysis aims to assess whether BOT was equally effective in adult EoE patients with and without prior use of STC (3).
Aims & Methods
This retrospective post-hoc analysis pooled 59 patients from the double-blind study phase of the BOT induction study (BUL-1) and 181 patients from the open-label induction phase of the BOT maintenance study (BUL-2). Patients were either STC-naïve (n=103) or had prior STC (n=118); for 19 patients previous treatment with STC was unknown. All patients received 1 mg BOT two times daily (BID) for 6 weeks. The primary efficacy end point was the rate of patients with clinico-histologic remission (≤2 points on numerical rating scales [0–10] each for dysphagia and odynophagia on each of the last 7 days prior to the end of treatment [EoT], and peak eosinophil count <16 eos/mm2 hpf [corresponding to <5 eos/hpf]) at week 6/EoT.
Results
BOT showed similar efficacy in patients both with and without prior STC treatment. Clinico-pathologic remission was recorded for 67.8% (n=67) of patients with prior STC treatment and 65% (n=80) of patients with no prior STC (table 1).
| Prior STC-treatment | Number (%) of patients achieving clinico-histological remission at week 6/EoT; [total number] |
| BUL-1 (1 mg BID) | BUL-2 (1 mg BID) | Overall |
| Unknown | 2 (66.7) [n=3] | 11 (68.8) [n=16] | 13 (68.4) [n=19] |
| No | 9 (52.9) [n=17] | 58 (67.4) [n=86] | 67 (65.0) [n=103] |
| Yes | 23 (59.0) [n=39] | 57 (72.2) [n=79] | 80 (67.8) [n=118] |
Conclusion
This post-hoc analysis of the BUL-1 and BUL-2 study program demonstrates that pre-treatment with STC other than BOT does not reduce the likelihood of achieving clinico-histological remission by treatment with BOT.
One explanation for successful induction of remission despite prior STC treatment is that initial relapse on STC may be due to insufficient delivery of STC to the esophageal mucosa, and/or insufficient equivalent dose of alternative topical steroid compound, rather than patients becoming truly corticosteroid-refractory. In addition, the specialized formulation of BOT that delivers budesonide precisely to the esophageal mucosa may also improve adherence, owing to a more standardized and convenient method of administration.
References
1. Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, et al. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology. 2019;157(1):74-86 e15.
2. Straumann A, Lucendo AJ, Miehlke S, Vieth M, Schlag C, Biedermann L, et al. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology. 2020;159(5):1672-85 e5.
3. Miehlke S, Hruz P, Vieth M, Bussmann C, von Arnim U, Bajbouj M, et al. A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut. 2016;65(3):390-9.
Disclosure
Philipp Schreiner reports fees for consulting/advisory board from AbbVie, BMS, Dr. Falk Pharma, Janssen, Pfizer, Takeda, Galapagos and Sanofi. Alfredo J Lucendo has received research funding from Dr Falk Pharma; Stephan Miehlke is a member of advisory boards for Celgene and EsoCap and has received speaker’s fee from Dr Falk Pharma GmbH and Falk Foundation. Ralph Mueller and Markus Kernbauer-Hölzl are employees of Dr Falk Pharma GmbH; Alain Schoepfer is a member of an advisory board for Dr Falk Pharma GmbH, Adare Pharmaceuticals, Celgene Pharmaceuticals, and Regeneron Pharmaceuticals. He has received research funding from Dr Falk Pharma GmbH, Adare Pharmaceuticals, Celgene Pharmaceuticals, and Regeneron Pharmaceuticals. He has received speaker’s fees from Dr Falk Pharma GmbH and Celgene Pharmaceuticals; Alex Straumann is a consultant of Calypso, EsoCap, Dr Falk Pharma GmbH, GSK, Receptos-Celgene, Regeneron-Sanofi, Shire and Tillotts, and has received speaker fees and research funding from Dr Falk Pharma GmbH. Luc Biedermann reports fees for consulting/advisory board from AbbVie, Amgen, BMS, MSD, Vifor, Dr. Falk Pharma, EsoCap, Janssen, Calypso, Ferring, Pfizer, Takeda, Janssen, and Sanofi.