Linaclotide Improves Abdominal Pain and Bowel Habits in a Phase IIb Study of Patients With Irritable Bowel Syndrome With Constipation

Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis

“…22 Despite the different impact on colorectal sensatory mechanisms, 19,[21][22][23] linaclotide, lubiprostone and tegaserod similarly alleviated chronic pain ratings in IBS-C and constipation. [9][10][11][24][25][26] The relationship between improved bowel patterns and decreased discomfort, as highlighted by our meta-analysis, does not establish an underlying mechanism, but fits into a larger context of past experimental and clinical data. As mentioned above, loperamide reduced bowel frequency in healthy volunteers to a degree sufficient to trigger symptoms consistent with IBS-C. 29 While few comparative effectiveness analyses of active agents are available, the limited evidence does not support superiority of more recently developed agents with polyethylene glycol (PEG) being either superior or equivalent to tegaserod.…”

“…Considering the defining role of pain and discomfort in IBS-C, a paradigm is evolving, which first examines efficacy in patients with chronic constipation, followed by trials in patients with IBS-C, which require more comprehensive assessments that demonstrate improvement beyond changes in bowel patterns. [9][10][11][12][13] The results of the newer studies demonstrated lower pain ratings during treatment and prompted speculations about specific analgesic effects of these agents, potentially differentiating them from more conventional laxatives, a feature that has been particularly highlighted in reviews and advertising campaigns. 14,15 Based largely on their impact on abdominal pain, the recently introduced pro-secretory agents (lubiprostone and linaclotide) were approved in the United States not only for the treatment of chronic constipation, but also specifically for the management of IBS-C, with marketing campaigns emphasizing their presumably unique benefits related to pain relief.…”

“…22 Despite the different impact on colorectal sensatory mechanisms, 19,[21][22][23] linaclotide, lubiprostone and tegaserod alleviated chronic pain ratings in IBS-C and constipation. [9][10][11][24][25][26] Interestingly, two studies compared the effects of tegaserod with polyethylene glycol (PEG), which acts as an osmotic laxative and should thus not directly affect sensory mechanisms or pain. However, the simple laxative was either superior to or demonstrated an equivalent effect to tegaserod.…”

Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome

“…In 2010 the results of a randomized phase IIb, double-blind, parallel group, placebo-controlled trial were published [Johnston et al 2010]. This was a multicentre study conducted in the United States and Canada, recruiting 420 patients with IBS-C as defined by the ROME II criteria.…”

Open Channels for Functional Bowel Disorders: Guanylate Cyclase C Agonists in IBS and CC

“…An increase in intracellular cGMP within intestinal epithelial cells activates CFTR, increasing the secretion of Cl -and HCO 3 -into the lumen, increasing the rate of plasmalumen water flux thereby increasing stool volume [3][4][5] in a mechanism identical to the diarrhea associated with In contrast to lubiprostone [6], linaclotide may stimulate motor activity [7]; lubiprostone, but not linaclotide, augments epithelial barrier resistance [8]. In IBS-C, linaclotide but not lubiprostone affects abdominal pain apparently independently of stool frequency [9], perhaps due to the effects of cGMP on visceral sensory afferents [10,11]. The combination of an acceleration of colonic transit with its visceral analgesic effect and increased stool volume bodes well for the clinical impact of linaclotide and related compounds in IBS-C.…”