title: Ramosetron Reduces Symptoms of Irritable Bowel Syndrome With Diarrhea and Improves Quality of Life in Women.
abstract: OBJECTIVE
  Previous studies have indicated that serotonin-3-receptor antagonists might have a sex-specific effect in patients with irritable bowel syndrome with diarrhea (IBS-D). Alosetron has been approved for the treatment of only women, and ramosetron has been approved for the treatment for only men. We performed a randomized, placebo-controlled, phase 3 study to determine whether ramosetron reduces symptoms of IBS-D in women.
  
  
  METHODS
  We performed a prospective study of 576 female outpatients with IBS-D (according to the Rome III criteria), from February 2013 through February 2014, at 70 academic Gastroenterology Departments in Japan. After a 1-week baseline period, subjects received either 2.5 μg ramosetron (n = 292) or placebo (n = 284) once daily for 12 weeks. Primary end points were the monthly rates of response for relief from overall IBS symptoms and increased stool consistency at the last evaluation point. Quality of life (QOL) also was quantified.
  
  
  RESULTS
  A significantly higher proportion of patients given ramosetron reported global improvement (50.7%; 95% confidence interval [CI], 44.8-56.6) than patients given placebo (32.0%; 95% CI, 26.7-37.8)--a difference of 18.6% (95% CI, 10.7-26.5; P < .001). The relative risk was 1.58 (95% CI, 1.29-1.94) and the number needed to treat was 6 (95% CI, 4-10). A significantly higher proportion of patients in the ramosetron group reported increased stool consistency (40.8%; 95% CI, 35.1%-46.6%) than in the placebo group (24.3%; 95% CI, 19.4%-29.7%)--a difference of 16.5% (95% CI, 8.9%-24.0%; P < .001). Patients receiving ramosetron had significant reductions in abdominal pain and discomfort (P = .001) and greater improvement in QOL (P = .002) compared with placebo. Ramosetron induced constipation in 11.0% of patients.
  
  
  CONCLUSIONS
  In a randomized, placebo-controlled study of 576 women with IBS-D, 2.5 μg ramosetron per day reduced symptoms and increased stool consistency and QOL. Clinicaltrials.gov no: NCT01870895.
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: sfukudo@med.tohoku.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Department of General Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Japan-Asia Planning and Administration, Medical and Development, Astellas Pharma, Inc, Tokyo, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Ida
authors.affiliation: Japan-Asia Clinical Development 2, Astellas Pharma, Inc, Tokyo, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Akiho
authors.affiliation: Japan-Asia Data Science, Astellas Pharma, Inc, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Development Project Management, Astellas Pharma, Inc, Tokyo, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Nishida
authors.affiliation: Department of Gastroenterology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
mesh_terms: D000328:Adult; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced; D003967:Diarrhea / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D007564:Japan; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012307:Risk Factors; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001562:Benzimidazoles; D005765:Gastrointestinal Agents; D058831:Serotonin 5-HT3 Receptor Antagonists; C071315:ramosetron
keywords: 5-HT; 5-Hydroxytryptamine-3–Receptor Antagonist; Abdominal Pain; Discomfort