Dose‐Dependent Effect of the Histamine 1 Receptor Antagonist Ebastine in Patients With Non‐Constipated Irritable Bowel Syndrome

BACKGROUND: Current treatment options for irritable bowel syndrome (IBS) mainly focus on restoring abnormal stool patterns but are less effective in relieving abdominal pain. Recent studies have identified mast cells as key players in visceral hypersensitivity (VHS) via histamine acting on histamine 1 receptor (H1R) activation. Our previous multicenter clinical trial showed clinical improvement of non-constipated IBS patients during treatment with 20 mg of the H1R-antagonist ebastine. Based on urticaria clinical trials showing increased symptom control with increased antihistamine dosage, we compared the effect of ebastine 20 mg vs. 40 mg in an open label study. METHODS: The effect of treatment of non-constipated IBS patients with ebastine 20 mg (n = 92) or 40 mg (n = 73) for 12 weeks was compared. Abdominal pain was assessed at baseline and at week 12 using a 10-point Visual Analogue Scale. Abdominal pain responders were defined as patients with at least 30% decrease in score compared to baseline, substantial abdominal pain responders with at least 50% reduction. Common gastrointestinal symptoms were evaluated using the GSRS questionnaire. KEY RESULTS: The percentage of abdominal pain responders and substantial abdominal pain responders was significantly increased with ebastine 40 mg compared to 20 mg (62% vs. 32%; p = 0.0014 and 40% vs. 12%; p = 0.0010, respectively). Moreover, the severity of diarrhea was significantly reduced with ebastine 40 mg (-1.0 (2.0) vs. 0.4 (1.8); p = 0.0334). CONCLUSIONS: Our study shows that ebastine 40 mg is more effective than 20 mg, resulting in increased symptom control, in particular reduction in abdominal pain, and supports further evaluation of ebastine as treatment of non-constipated IBS.