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

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.