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Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation.
Clin Gastroenterol Hepatol 2014; 12(4):616-23CG

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.

Authors+Show Affiliations

Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia.Gastroenterology Division, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.Forest Research Institute, Jersey City, New Jersey.Ironwood Pharmaceuticals, Cambridge, Massachusetts.Ironwood Pharmaceuticals, Cambridge, Massachusetts.Ironwood Pharmaceuticals, Cambridge, Massachusetts.Ironwood Pharmaceuticals, Cambridge, Massachusetts.Ironwood Pharmaceuticals, Cambridge, Massachusetts. Electronic address: jjohnston@ironwoodpharma.com.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24075889

Citation

Rao, Satish S C., et al. "Effect of Linaclotide On Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, vol. 12, no. 4, 2014, pp. 616-23.
Rao SS, Quigley EM, Shiff SJ, et al. Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clin Gastroenterol Hepatol. 2014;12(4):616-23.
Rao, S. S., Quigley, E. M., Shiff, S. J., Lavins, B. J., Kurtz, C. B., MacDougall, J. E., ... Johnston, J. M. (2014). Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 12(4), pp. 616-23. doi:10.1016/j.cgh.2013.09.022.
Rao SS, et al. Effect of Linaclotide On Severe Abdominal Symptoms in Patients With Irritable Bowel Syndrome With Constipation. Clin Gastroenterol Hepatol. 2014;12(4):616-23. PubMed PMID: 24075889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. AU - Rao,Satish S C, 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, Y1 - 2013/09/25/ PY - 2013/06/10/received PY - 2013/09/06/revised PY - 2013/09/08/accepted PY - 2013/10/1/entrez PY - 2013/10/1/pubmed PY - 2014/11/5/medline KW - Abdominal Pain KW - Bloating KW - Guanylate Cyclase-C KW - IBS-C SP - 616 EP - 23 JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin. Gastroenterol. Hepatol. VL - 12 IS - 4 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. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/24075889/Effect_of_linaclotide_on_severe_abdominal_symptoms_in_patients_with_irritable_bowel_syndrome_with_constipation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1542-3565(13)01427-4 DB - PRIME DP - Unbound Medicine ER -