Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome

Abstract

Toshimi Chiba, Kazunari Yamamoto, Shoko Sato, Kazuyuki Suzuki Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan Abstract: Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 µg and 10 µg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 µg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001). Furthermore, the responder rate was increased in the oral administration of 5 µg of ramosetron for at least 28 weeks (up to 52 weeks), and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in ramosetron treatment. No serious adverse events, eg, severe constipation or ischemic colitis, were reported for long-term treatment with ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of ramosetron are warranted in the form of randomized controlled trials. Keywords: long-term efficacy, safety, ramosetron, irritable bowel syndrome