Efficacy of otilonium bromide in irritable bowel syndrome: a pooled analysis

Abstract

Background: Otilonium bromide (OB) is a spasmolytic agent acting as an L-type calcium channel antagonist in intestinal and colonic smooth muscle cells (SMCs). We analyzed three independent clinical trials with homogeneous design on patients with irritable bowel syndrome (IBS). After 2 weeks receiving placebo, patients were randomized to receive OB (3 × 40 mg daily) or placebo for 15 weeks. We aimed to perform a pooled analysis of the data from these homogeneous clinical trials to evaluate the efficacy of OB treatment on symptoms and global response of patients.

Methods: A total of 883 patients with IBS (69.8% women, mean age 46.2 years, 43.8% mixed type) were included, 442 treated with OB and 441 with placebo. The efficacy results from the three studies at weeks 5, 10 and 15 were pooled in an intention-to-treat (ITT) strategy, analyzed with a logistic regression model and described by forest plots.

Results: Despite a placebo effect in all efficacy variables, a significant therapeutic effect of OB was observed at weeks 10 and 15 with reference to: (a) intensity and frequency of abdominal pain; (b) rate of responders as evaluated by patients (71.8% at week 10 and 77.2% at week 15); (c) severity of bloating; (d) rate of responders as evaluated by physicians (55% at week 10 and 63.9% at week 15). No significant OB effect was observed in stool frequency and consistency.

Conclusions: OB is more effective than placebo in IBS treatment. Therapeutic benefits are significant after 10 weeks and are maximal after 15 weeks of treatment.

Keywords: abdominal pain; bloating; distention; global response; intention-to-treat analysis; irritable bowel syndrome; otilonium bromide.

Figure 1.

Reduction (difference versus baseline) of abdominal pain intensity score (ITT pooled dataset). p = ANOVA p-value. *p < 0.05 in the GLM (both significant at week 10 and 15). ANOVA, analysis of variance; GLM, general linear model; ITT, intention-to-treat; OB, otilonium bromide.

Figure 2.

Forest plots including results from the pooled analysis on the primary efficacy variables from Battaglia and colleagues [Battaglia et al. 1998], OBIS [Clave et al. 2011], and Greek [Menarini IFR, 2012] studies. (a) Responder patients according to intensity of pain evaluated by the patient (ITT pooled dataset, week 15); (b) Responder patients according to number of episodes of abdominal pain evaluated by the patient (ITT pooled dataset, week 15); (c) Responder patients according to global evaluation of pain evaluated by the patient (ITT pooled dataset, week 15); (d) Responder patients according to severity of bloating score evaluated by the patient (ITT pooled dataset, week 15); (e) Responder patients according to global efficacy assessment evaluated by the physician. ITT, intention-to-treat; OB, otilonium bromide.

Figure 3.

Reduction of the number of episodes of abdominal pain score (ITT pooled dataset). p = ANOVA p-value. *p < 0.05 in the GLM at week 15. ANOVA, analysis of variance; GLM, general linear model; ITT, intention-to-treat; OB, otilonium bromide.

Figure 4.

Reduction of the global evaluation of pain index (ITT pooled dataset). p = ANOVA p-value. *p < 0.05 in the GLM at week 15. ANOVA, analysis of variance; GLM, general linear model; ITT, intention-to-treat; OB, otilonium bromide.

Figure 5.

Reduction of stool frequency (ITT pooled dataset). p = ANOVA p-value. ANOVA, analysis of variance; ITT, intention-to-treat; OB, otilonium bromide.

Figure 6.

Reduction (difference versus baseline) of severity of bloating-meteorism score (ITT dataset). p = ANOVA p-value. *p < 0.05 in the GLM at week 10 and 15. ANOVA, analysis of variance; GLM, general linear model; ITT, intention-to-treat; OB, otilonium bromide.