Effect of Linaclotide on Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation

Satish Sanku Chander Rao, Eamonn M.M. Quigley, Steven J. Shiff, Bernard J. Lavins, Caroline B. Kurtz, James E. MacDougall, Mark G. Currie, Jeffrey M. Johnston

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background & Aims: Patients with irritable bowel syndrome with constipation (IBS-C) have abdominal symptoms that vary in severity. Linaclotide, a guanylate cyclase-C agonist, improves abdominal and bowel symptoms in these patients. We examined the prevalence of severe abdominal symptoms in patients with IBS-C and assessed the effects of linaclotide on abdominal symptoms, global measures, and quality of life (QOL). Methods: In two phase 3 trials, patients who met modified Rome II criteria for IBS-C were randomly assigned to groups given oral, once-daily linaclotide (290 μg) or placebo for 12 weeks. During the baseline (2 weeks prior to treatment) and treatment periods, patients rated abdominal pain, discomfort, bloating, fullness, and cramping daily (from 0= none to 10= very severe). Linaclotide's effects on abdominal symptoms, global measures, and IBS-related QOL were assessed in subpopulations of patients who rated specific individual abdominal symptoms as severe (≥7.0) at baseline. Results: In the intent-to-treat population (1602 patients; 797 receiving placebo and 805 receiving linaclotide), baseline prevalence values for severe abdominal symptoms were 44% for bloating, 44% for fullness, 32% for discomfort, 23% for pain, and 22% for cramping, with considerable overlap among symptoms. In patients with severe symptoms, linaclotide reduced all abdominal symptoms; mean changes from baseline severity scores ranged from -2.7 to -3.4 for linaclotide vs -1.4 to -1.9 for placebo (P < .0001). Linaclotide improved global measures (P < .0001) and IBS-QOL scores (P < .01) compared with placebo. Diarrhea was the most common adverse event of linaclotide in patients with severe abdominal symptoms (18.8%-21.0%). Conclusions: Of 5 severe abdominal symptoms assessed, bloating and fullness were most prevalent in patients with IBS-C. Linaclotide significantly improved all abdominal symptoms, global measures, and IBS-QOL in subpopulations of IBS-C patients with severe abdominal symptoms. Clinicaltrials.gov Numbers: NCT00938717, NCT00948818.

Original languageEnglish (US)
Pages (from-to)616-623
Number of pages8
JournalClinical Gastroenterology and Hepatology
Volume12
Issue number4
DOIs
StatePublished - Jan 1 2014

Fingerprint

Irritable Bowel Syndrome
Constipation
Placebos
Quality of Life
linaclotide
Guanylate Cyclase
Abdominal Pain
Diarrhea
Pain

Keywords

  • Abdominal pain
  • Bloating
  • Guanylate cyclase-C
  • IBS-C

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Effect of Linaclotide on Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation. / Rao, Satish Sanku Chander; Quigley, Eamonn M.M.; Shiff, Steven J.; Lavins, Bernard J.; Kurtz, Caroline B.; MacDougall, James E.; Currie, Mark G.; Johnston, Jeffrey M.

In: Clinical Gastroenterology and Hepatology, Vol. 12, No. 4, 01.01.2014, p. 616-623.

Research output: Contribution to journalArticle

Rao, SSC, Quigley, EMM, Shiff, SJ, Lavins, BJ, Kurtz, CB, MacDougall, JE, Currie, MG & Johnston, JM 2014, 'Effect of Linaclotide on Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation', Clinical Gastroenterology and Hepatology, vol. 12, no. 4, pp. 616-623. https://doi.org/10.1016/j.cgh.2013.09.022
Rao, Satish Sanku Chander ; Quigley, Eamonn M.M. ; Shiff, Steven J. ; Lavins, Bernard J. ; Kurtz, Caroline B. ; MacDougall, James E. ; Currie, Mark G. ; Johnston, Jeffrey M. / Effect of Linaclotide on Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation. In: Clinical Gastroenterology and Hepatology. 2014 ; Vol. 12, No. 4. pp. 616-623.
@article{c69dc37f7a7542beba3f9e6856a5e3fd,
title = "Effect of Linaclotide on Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation",
abstract = "Background & Aims: Patients with irritable bowel syndrome with constipation (IBS-C) have abdominal symptoms that vary in severity. Linaclotide, a guanylate cyclase-C agonist, improves abdominal and bowel symptoms in these patients. We examined the prevalence of severe abdominal symptoms in patients with IBS-C and assessed the effects of linaclotide on abdominal symptoms, global measures, and quality of life (QOL). Methods: In two phase 3 trials, patients who met modified Rome II criteria for IBS-C were randomly assigned to groups given oral, once-daily linaclotide (290 μg) or placebo for 12 weeks. During the baseline (2 weeks prior to treatment) and treatment periods, patients rated abdominal pain, discomfort, bloating, fullness, and cramping daily (from 0= none to 10= very severe). Linaclotide's effects on abdominal symptoms, global measures, and IBS-related QOL were assessed in subpopulations of patients who rated specific individual abdominal symptoms as severe (≥7.0) at baseline. Results: In the intent-to-treat population (1602 patients; 797 receiving placebo and 805 receiving linaclotide), baseline prevalence values for severe abdominal symptoms were 44{\%} for bloating, 44{\%} for fullness, 32{\%} for discomfort, 23{\%} for pain, and 22{\%} for cramping, with considerable overlap among symptoms. In patients with severe symptoms, linaclotide reduced all abdominal symptoms; mean changes from baseline severity scores ranged from -2.7 to -3.4 for linaclotide vs -1.4 to -1.9 for placebo (P < .0001). Linaclotide improved global measures (P < .0001) and IBS-QOL scores (P < .01) compared with placebo. Diarrhea was the most common adverse event of linaclotide in patients with severe abdominal symptoms (18.8{\%}-21.0{\%}). Conclusions: Of 5 severe abdominal symptoms assessed, bloating and fullness were most prevalent in patients with IBS-C. Linaclotide significantly improved all abdominal symptoms, global measures, and IBS-QOL in subpopulations of IBS-C patients with severe abdominal symptoms. Clinicaltrials.gov Numbers: NCT00938717, NCT00948818.",
keywords = "Abdominal pain, Bloating, Guanylate cyclase-C, IBS-C",
author = "Rao, {Satish Sanku Chander} and Quigley, {Eamonn M.M.} and Shiff, {Steven J.} and Lavins, {Bernard J.} and Kurtz, {Caroline B.} and MacDougall, {James E.} and Currie, {Mark G.} and Johnston, {Jeffrey M.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.cgh.2013.09.022",
language = "English (US)",
volume = "12",
pages = "616--623",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Effect of Linaclotide on Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation

AU - Rao, Satish Sanku Chander

AU - Quigley, Eamonn M.M.

AU - Shiff, Steven J.

AU - Lavins, Bernard J.

AU - Kurtz, Caroline B.

AU - MacDougall, James E.

AU - Currie, Mark G.

AU - Johnston, Jeffrey M.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background & Aims: Patients with irritable bowel syndrome with constipation (IBS-C) have abdominal symptoms that vary in severity. Linaclotide, a guanylate cyclase-C agonist, improves abdominal and bowel symptoms in these patients. We examined the prevalence of severe abdominal symptoms in patients with IBS-C and assessed the effects of linaclotide on abdominal symptoms, global measures, and quality of life (QOL). Methods: In two phase 3 trials, patients who met modified Rome II criteria for IBS-C were randomly assigned to groups given oral, once-daily linaclotide (290 μg) or placebo for 12 weeks. During the baseline (2 weeks prior to treatment) and treatment periods, patients rated abdominal pain, discomfort, bloating, fullness, and cramping daily (from 0= none to 10= very severe). Linaclotide's effects on abdominal symptoms, global measures, and IBS-related QOL were assessed in subpopulations of patients who rated specific individual abdominal symptoms as severe (≥7.0) at baseline. Results: In the intent-to-treat population (1602 patients; 797 receiving placebo and 805 receiving linaclotide), baseline prevalence values for severe abdominal symptoms were 44% for bloating, 44% for fullness, 32% for discomfort, 23% for pain, and 22% for cramping, with considerable overlap among symptoms. In patients with severe symptoms, linaclotide reduced all abdominal symptoms; mean changes from baseline severity scores ranged from -2.7 to -3.4 for linaclotide vs -1.4 to -1.9 for placebo (P < .0001). Linaclotide improved global measures (P < .0001) and IBS-QOL scores (P < .01) compared with placebo. Diarrhea was the most common adverse event of linaclotide in patients with severe abdominal symptoms (18.8%-21.0%). Conclusions: Of 5 severe abdominal symptoms assessed, bloating and fullness were most prevalent in patients with IBS-C. Linaclotide significantly improved all abdominal symptoms, global measures, and IBS-QOL in subpopulations of IBS-C patients with severe abdominal symptoms. Clinicaltrials.gov Numbers: NCT00938717, NCT00948818.

AB - Background & Aims: Patients with irritable bowel syndrome with constipation (IBS-C) have abdominal symptoms that vary in severity. Linaclotide, a guanylate cyclase-C agonist, improves abdominal and bowel symptoms in these patients. We examined the prevalence of severe abdominal symptoms in patients with IBS-C and assessed the effects of linaclotide on abdominal symptoms, global measures, and quality of life (QOL). Methods: In two phase 3 trials, patients who met modified Rome II criteria for IBS-C were randomly assigned to groups given oral, once-daily linaclotide (290 μg) or placebo for 12 weeks. During the baseline (2 weeks prior to treatment) and treatment periods, patients rated abdominal pain, discomfort, bloating, fullness, and cramping daily (from 0= none to 10= very severe). Linaclotide's effects on abdominal symptoms, global measures, and IBS-related QOL were assessed in subpopulations of patients who rated specific individual abdominal symptoms as severe (≥7.0) at baseline. Results: In the intent-to-treat population (1602 patients; 797 receiving placebo and 805 receiving linaclotide), baseline prevalence values for severe abdominal symptoms were 44% for bloating, 44% for fullness, 32% for discomfort, 23% for pain, and 22% for cramping, with considerable overlap among symptoms. In patients with severe symptoms, linaclotide reduced all abdominal symptoms; mean changes from baseline severity scores ranged from -2.7 to -3.4 for linaclotide vs -1.4 to -1.9 for placebo (P < .0001). Linaclotide improved global measures (P < .0001) and IBS-QOL scores (P < .01) compared with placebo. Diarrhea was the most common adverse event of linaclotide in patients with severe abdominal symptoms (18.8%-21.0%). Conclusions: Of 5 severe abdominal symptoms assessed, bloating and fullness were most prevalent in patients with IBS-C. Linaclotide significantly improved all abdominal symptoms, global measures, and IBS-QOL in subpopulations of IBS-C patients with severe abdominal symptoms. Clinicaltrials.gov Numbers: NCT00938717, NCT00948818.

KW - Abdominal pain

KW - Bloating

KW - Guanylate cyclase-C

KW - IBS-C

UR - http://www.scopus.com/inward/record.url?scp=84896082720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896082720&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2013.09.022

DO - 10.1016/j.cgh.2013.09.022

M3 - Article

VL - 12

SP - 616

EP - 623

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 4

ER -