Loss of Response to Off-Label Swallowed Topical Corticosteroids in Eosinophilic Esophagitis Can be Overcome by a Switch to an Esophageal-Targeted Budesonide Formulation.

Introduction: Swallowed topical corticosteroids (STCs) are effective in treating patients with eosinophilic esophagitis. However, real-world data about loss of response to STC are limited and whether patients with off-label STC (olSTC) failure may achieve histologic remission after a switch to budesonide orodispersible tablets (BOT) is unknown.

Methods: We analyzed prospectively collected data between 2015 and 2023 from the Swiss Eosinophilic Esophagitis Cohort Study and compared patients with prior histologic olSTC-failure (≥15 eosinophils per high-power field), histologic remission after olSTC (<15 eosinophils per high-power field), and STC-naïve patients before BOT treatment. Furthermore, we evaluated the course of olSTC-failure patients after a switch to BOT and used logistic regression to explore potential associations between patients with olSTC-failure and clinical factors.

Results: A total of 340 patients (76% male, median age = 43 years) with BOT were analyzed. Twenty-six percent had prior olSTC nonresponse, 16% were in remission with prior olSTC, and 58% were STC-naïve. In the multivariable logistic regression, olSTC treatment duration in years (OR 1.37, 95% CI 1.12-1.67, P = 0.002), off-label STC adherence <80% in the last 2 years before BOT (6.30; 1.19-33.29, P = 0.03), and age <30 years (6.57; 1.85-23.37, P = 0.004) were independently associated with histologic nonresponse to olSTC. Histologic or combined remission to BOT was not different in patients with prior olSTC response (n = 44) compared to patients nonresponded to olSTC (n = 66) (77.3% vs 62.1%, P = 0.095 and 61.4% vs 42.4%, P = 0.052).

Discussion: Most patients nonresponding to olSTC are not true corticosteroid-refractory but respond to an esophageal-targeted budesonide formulation. Age below 30 years, longer treatment duration and low adherence are associated with olSTC-failure.