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Small bowel II
PWE-127 Two randomised, double-blind, placebo-controlled phase 3 trials of linaclotide in adults with irritable bowel syndrome: effects on quality of life
  1. R T Carson1,
  2. S Tourkodimitris1,
  3. B E Lewis2,
  4. J M Johnston2
  1. 1Forest Research Institute, Jersey City, New Jersey, USA
  2. 2Ironwood Pharmaceuticals, Cambridge, USA

Abstract

Introduction Linaclotide, a minimally absorbed guanylate cyclase-C receptor agonist, is an investigational drug for the treatment of irritable bowel syndrome with constipation (IBS-C) that has shown statistically significant improvements in abdominal and bowel symptoms in two Phase 3 clinical trials. IBS-C is a common functional gastrointestinal disorder that affects a significant portion of the population and leads to reduced quality of life (QOL).

Methods Data evaluating the efficacy and safety of oral once-daily linaclotide 290 μg (N=748) vs placebo (N=742) in patients with IBS-C were pooled from two Phase 3 clinical trials. Patients meeting modified Rome II criteria for IBS-C were randomised to receive either linaclotide or placebo treatment for 12 weeks. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire, comprising 34 items, each with a 5-point response scale (1= “not at all” through to 5= “extremely” or “a great deal”), was completed at baseline and also at the end of the treatment period. The IBS-QOL is scored “overall” and by eight subscales (Dysphoria, Interference with Activity, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual and Relationships). The change from baseline to week 12 scores were analysed using an analysis of covariance model. The IBS-QOL response rates (ie, patients with ≥10-point and ≥14-point increase) for the treatment groups were compared using Cochran-Mantel-Haenszel stratified by geographical region.

Results The changes from baseline in the IBS-QOL “overall” score and seven of the eight subscale scores (Dysphoria, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual and Relationships) were statistically significant for linaclotide-treated patients vs placebo-treated patients (p<0.0001 for each comparison). The percentage of responders for the IBS-QOL “overall” score was statistically significantly greater for linaclotide-treated patients vs placebo-treated patients at week 12 (64.3% linaclotide-treated patients vs 52.6% placebo-treated patients for ≥10-point change; 53.8% linaclotide-treated patients vs 39.1% placebo-treated patients for ≥14-point change). The most common adverse event among linaclotide-treated patients was diarrhoea.

Conclusion Compared with placebo, once-daily linaclotide treatment for 12 weeks significantly improved “overall” QOL scores and seven out of eight important QOL domains, as measured by the IBS-QOL, in adults with IBS-C.

Competing interests R T Carson Employee of: Forest Research Institute, S Tourkodimitris Employee of: Forest Research Institute, B E Lewis Employee of: Ironwood Pharmaceuticals, J M Johnston Employee of: Ironwood Pharmaceuticals.

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