Introduction

Swallowed topical corticosteroids (STC) mostly based on fluticasone propionate (FP) and budesonide (Bud) formulations, are extensively used to induce and maintain remission of eosinophilic esophagitis (EoE) (1). SCT consist mainly of metered-dose inhaled or spray, applied in the mouth and then swallowed (MDIS), suspension of nasal drops, swallowed instead of applied inside the nose (SND), oral viscous syrups prepared by pharmacists (OVSP), and marketed oral disintegrating tables (ODT) (2).

Aims & Methods

The study aims to compare the effectiveness of different STC formulations in real-world clinical practice. Data on STC used in the first five lines of therapy (drug, formulation, dosage and effectiveness) were extracted from EUREOS EoE CONNECT registry (3),^​ provided by patients from 31 hospitals. STC treatments performed under a double blinded phase of a clinical trial were not considered for effectiveness analyses. Clinical remission was defined by a decrease >50% in the Dysphagia Symptom Score and/or according to clinician criteria. Histological remission was defined as a peak of eosinophil count <15 eosinophils/HPF after treatment. Clinico-histological remission (CHR) was present when both responses concurred and was used as effectiveness criterion. Statistical significance was established for p<0.05.

Results

Overall, 1,456 prescriptions of STC in monotherapy were analyzed. The use of STC increased as the line of treatment progressed, from 9% in 1st-line to 48% in the 5th-line therapy (p<0.001), as it did Bud prescriptions, from 29% in first-line SCT therapy to 54% in fifth-line (p<0.001).
Overall, 915 STC induction treatments with full data of formulation and dosage were analyzed. FP predominated over Bud (58% vs 42%). The most common FP formulation was SND (74%) at an 800 µg/daily dose (69% of SND). This dosage was superior to 400 µg/day (12% of SND) to induce CHR (66% vs 30%, p<0.001); However, 1,600 µg/day provided no additional advantage (17% of SND, 58% of CHR). The second most used FP formulation was MDIS (24%) at 1 mg/daily (46% of MDIS), which induced CHR in 60%, higher than that achieved with a 0.5 mg/daily dose (30% of MDIS, 41% of CHR), despite not significant (p=0.24).
Among Bud-based therapies, OVSP were the most common formulations (56%) followed by ODT (25%), prescribed at 2 mg/daily doses (69% and 56%, respectively). A 1 mg/daily dose (7% of OVSP and 44% of ODT prescriptions) was less effective than the 2 mg/daily dose in achieving histologic remission: for OVSP, 1mg/day and 2mg/day induced CHR in 64% and 80% of patients, respectively (p=0.25); for ODT 1 mg/day and 2 mg/day induced CHR respectively in 86% and 100% of patients (p=0.04). In contrast, using Bud 4 mg/daily OVSP resulted not superior to 2 mg/daily (CHR rate being 72%). When all induction regimes were compared, Bud resulted overall superior to FP to achieve CHR (82% vs 60%, p<0.001).
We evaluated 236 maintenance treatments (53% FP and 47% Bud) in which induction doses were reduced after being effective in CHR induction. FP SND at 400 µg/day achieved a CHR in 46%; MDIS formulations were barely used for this purpose. Bud at 1 mg/day was effective in 68% of OVSP and 67% of ODT dose reductions. When all dose reductions of FP and Bud as first maintenance therapy were compared, CHR was higher for the latter (46% vs 69%, p<0.01).

Conclusion

Most appropriate STC to induce EoE remission consists of FP SND at 800 µg/day, FP MDIS at 1 mg/day, and Bud (OVSP or ODT) at 2 mg/daily. Reduction to half of these dosages was more effective for Bud formulations.

References

1. Arias A & Lucendo AJ. Epidemiology and risk factors for eosinophilic esophagitis: lessons for clinicians. Expert Rev Gastroenterol Hepatol. 2020;14(11):1069-82.
2. Nennstiel S & Schlag C. Treatment of eosinophilic esophagitis with swallowed topical corticosteroids. World J Gastroenterol. 2020;26(36):5395-407.
3. Lucendo AJ, et al. EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe. Therap Adv Gastroenterol. 2022;15:17562848221074204.

Disclosure

AJ Lucendo has served as a speaker, and/or has received research and/or education funding and/or consulting fees from Adare/Ellodi, Dr. Falk Pharma, Regeneron, Dr. Falk Pharma and EsoCap. C. Santander received honoraria as consultant and trainer at Laborie/MMS and Medtronic Covidien AG, and received research funding from AstraZeneca, EsoCap Biotech, Regeneron Pharmaceuticals Inc., Adare Pharmaceuticals Inc., and Dr. Falk Pharma GmbH. J. Alcedo has served as a speaker, consultant and advisory member for or has received research funding from Adare Pharmaceuticals Inc, Abbvie, MSD, Allergan, and Shire Pharmaceuticals. C. Gutiérrez-Junquera has received research funding from Dr. Falk Pharma. The remaining authors have no conflict of interest.