Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation.
OBJECTIVE
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


METHODS
NCT00938717, NCT00948818.
Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia.
Satish S C
SS
Rao
Gastroenterology Division, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.
Eamonn M M
EM
Quigley
Forest Research Institute, Jersey City, New Jersey.
Steven J
SJ
Shiff
Ironwood Pharmaceuticals, Cambridge, Massachusetts.
Bernard J
BJ
Lavins
Ironwood Pharmaceuticals, Cambridge, Massachusetts.
Caroline B
CB
Kurtz
Ironwood Pharmaceuticals, Cambridge, Massachusetts.
James E
JE
MacDougall
Ironwood Pharmaceuticals, Cambridge, Massachusetts.
Mark G
MG
Currie
Ironwood Pharmaceuticals, Cambridge, Massachusetts. Electronic address: jjohnston@ironwoodpharma.com.
Jeffrey M
JM
Johnston
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003248:Constipation / Q000188:drug therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D005765:Gastrointestinal Agents; D010455:Peptides; D010919:Placebos; C523483:linaclotide
Abdominal Pain; Bloating; Guanylate Cyclase-C; IBS-C