Swallowed Topical Tacrolimus Induces Clinical and Histological Remission in a Subset of Patients with Severe Lymphocytic Esophagitis.

Abstract

Introduction: Lymphocytic esophagitis (LyE) represents a chronic inflammatory disease of the esophagus with low response rates to topical steroids. Thus, novel treatment options such as swallowed topical tacrolimus, particularly for refractory cases, are urgently needed.

Methods: We retrospectively analyzed patients with LyE enrolled in the Swiss eosinophilic esophagitis database that received treatment with a swallowed tacrolimus syrup (1 mg bid). We compared clinical (visual analogue scale [VAS] 0-10), endoscopic (VAS, Endoscopic Reference Score [EREFS]), and histological (peak lymphocyte count) disease activity before versus after treatment.

Results: Out of 17 LyE patients, we identified a total of 7 patients undergoing tacrolimus treatment (4 males, median age 71.3 years, IQR: 61.3-76.5, median diagnostic delay of 51.0 months, IQR: 24.5-62.0). Six patients had been previously treated with PPI, five with topical and/or systemic steroids. All patients were treated with topical tacrolimus corresponding to 1 mg bid (for a median of 13 weeks, IQR: 11-15). All patients had clinically, and histologically active disease at baseline. Topical tacrolimus treatment resulted in histological remission (<30 lymphocytes/hpf) in 3/7 patients (42.9%), while 4/7 patients achieved symptomatic remission (VAS for dysphagia ≤2, 57.1%). Overall, clinical (VAS 5 vs. 2, p = 0.0625) and endoscopic activity (VAS 5 vs. 2, p = 0.0625, and EREFS 3 vs. 2, p = 0.125) decreased. Measurement of tacrolimus trough levels in 4/7 patients (range 2.1-3.9 μg/L) revealed some degree of systemic absorption. Mild adverse events to the tacrolimus treatment were seen in 2 patients (esophageal candidiasis, hyposensitivity around lips). No impact on kidney function was observed during the treatment period.

Conclusion: Topical tacrolimus appears to be a potential treatment option for severe LyE, particularly after failure of PPI and/or topical steroids. Further studies are needed, in particular regarding the optimal galenic formulation to avoid systemic absorption.