Evaluation of the irritable bowel syndrome severity index in Japanese male patients with irritable bowel syndrome with diarrhea

Motoko Ida, Akito Nishida, Hiraku Akiho, Yoshihiro Nakashima, Kei Matsueda, Shin Fukudo, Motoko Ida, Akito Nishida, Hiraku Akiho, Yoshihiro Nakashima, Kei Matsueda, Shin Fukudo

Abstract

Background: Previous studies have indicated that ramosetron, a 5-hydroxytryptamine-3 receptor antagonist, achieves global improvement in irritable bowel syndrome (IBS) symptoms in male patients with IBS with diarrhea (IBS-D). However, in addition to global assessment it was deemed important to assess "clinically meaningful improvements, focusing on the patient's chief complaint and the severity of major IBS symptoms". We performed a randomized, placebo-controlled, phase IV pilot study to explore and examine efficacy variables that allow such evaluation of ramosetron in male patients with IBS-D.

Methods: We performed a prospective study of 115 male outpatients with IBS-D (according to the Rome III criteria), from June 2009 to December 2009 at 25 centers in Japan. After a one-week baseline period, subjects received either 5 μg of ramosetron (n = 47) or placebo (n = 51) once daily for 12 weeks. To evaluate "clinically meaningful improvements focusing on the severity of major IBS symptoms," the Japanese version of the IBS severity index (IBSSI-J) was used.

Results: Change in IBSSI-J overall score from baseline was -133.5 ± 110.72 in the ramosetron 5 μg group and -108.2 ± 94.44 in the placebo group (P = 0.228) at the last evaluation point. Differences in responder rates for at least a 50% reduction from baseline in IBSSI-J between the ramosetron 5 μg group and the placebo group were over 10%, except Month 1. The monthly responder rate for global assessment of relief of overall IBS symptoms in the ramosetron 5 μg group showed a statistically significant improvement compared to placebo at the second month (44.4% vs 18.4%, P = 0.012). The proportion of patients who had a ≥ 50% reduction in IBSSI-J overall score was 24/37 (64.9%) in the responder group on global assessment and 18/54 (33.3%) in the non-responder group at Week 12.

Conclusions: Further examination will be needed before IBSSI-J can be used in clinical trials of agents for IBS-D. However, this study revealed that response on global assessment was correlated with improvement in the IBSSI-J, suggesting that global assessment reflects improvement of the symptom severity of patients with IBS-D. (Clinicaltrials.gov ID: NCT00918411 Registered 9 June 2009).

Keywords: 5-hydroxytryptamine (5-HT); Abdominal discomfort; Abdominal pain; Global improvement; Irritable bowel syndrome severity index; Stool consistency.

Figures

Fig. 1
Fig. 1
Flowchart showing patient progress throughout the study. Reasons for dropping out of the study are shown
Fig. 2
Fig. 2
Change in IBSSI-J overall scores. a Change in IBSSI-J overall scores from baseline, adjusted by baseline score. Column height: the values adjusted using the baseline score as a covariate. Error bar: 95% CI. P values were calculated using analysis of covariance with the treatment group as a factor and baseline score as a covariate. b Responder rates for at least a 50% reduction from baseline in IBSSI-J overall score. Column height: responder rate (%). Error bar: 95% CI
Fig. 3
Fig. 3
Global assessments. a Monthly responder rates for global assessments of relief of overall IBS symptoms. b Monthly responder rates for improvement in abnormal bowel habits. Column height: responder rate (%). Error bar: 95% CI. P values were calculated using the chi-square test, as follows: *P < 0.05
Fig. 4
Fig. 4
Relationship between IBSSI-J and global assessment. a Changes in IBSSI-J overall scores from baseline were compared by responder/non-responder for global assessment of relief of overall IBS symptoms. Mean changes in IBSSI-J overall scores from baseline were categorized into the following groups: ≤ −200, −200 < and ≤ −80, −80 < and ≤ −50, −50 < and ≤ 0, 0 <. b Percent change in IBSSI-J overall score from baseline was compared by responder/non-responder for global assessment of relief of overall IBS symptoms. Percent change in IBSSI-J from baseline was categorized into the following groups: ≤ −75, −75 < and ≤ −50, −50 < and ≤ −30, −30 < and ≤ 0 and 0 <

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