Efficacy of Linaclotide for Patients With Chronic Constipation

Lembo, Anthony; Kurtz, Caroline B.; MacDougall, James E.; Lavins, Bernard J.; Currie, Mark G.; Fitch, Donald A.; Jeglinski, Brenda I.; Johnston, Jeffrey M.

doi:10.1053/j.gastro.2009.12.050

Cited by 211 publications

(132 citation statements)

References 24 publications

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“…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.…”

Section: Discussionmentioning

confidence: 94%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Bielefeldt

Levinthal

Nusrat

2015

J Neurogastroenterol Motil

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Background/AimsThe marketing of newer agents for treatment of constipation and irritable bowel syndrome with constipation (IBS-C) emphasize improvements in abdominal pain. However, it is not clear whether this observation reflects a unique visceral analgesic effect of these agents or is a general feature of effective laxation. We sought to determine the relationship between improvements in bowel frequency and decreases in abdominal pain in clinical trials of patients with constipation or IBS-C. MethodsWe searched "PubMed" and "Embase" databanks for clinical trials in patients with constipation or IBS-C, targeting publications that provided detailed data on bowel movement frequency and pain intensity before and after an intervention. We abstracted the results and performed meta-analytic and meta-regression analyses. Results Twenty

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Bielefeldt

Levinthal

Nusrat

2015

J Neurogastroenterol Motil

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“…Linaclotide, a non-absorbed substance approved for the treatment of constipation and irritable bowel syndrome with constipation (IBS-C), acts by binding to this specific receptor. An intracellular cascade of events leads to activation of chloride secretion and thereby a net movement of water into the gut lumen, resulting in softer stool and more frequent bowel movements [27]. A feature of particular interest relates to reductions in constipation associated abdominal pain [28] and bloating [29], which can develop gradually over months from the start of treatment.…”

Section: Constipationmentioning

confidence: 99%

Treatment of gastrointestinal autonomic neuropathy

Törnblom

2015

Diabetologia

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The symptoms caused by gastrointestinal autonomic neuropathy in diabetes mellitus is important to highlight since it affects a large proportion of people with diabetes, regardless of whether this is type 1 or type 2. Gastroparesis and general signs of bowel dysfunction, such as constipation, diarrhoea and abdominal pain are most often encountered and involve both pharmacological and non-pharmacological treatment options. This mini-review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Azpiroz and Malagelada,

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“…Following the previous study, a phase IIb multicentre, randomized, double-blind, placebo-controlled trial was conducted in 310 patients with CIC [Lembo et al 2010]. The study was conducted at 57 clinical centres in the USA.…”

Section: Phase Iib Studymentioning

confidence: 99%

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

Sood

Ford

2013

Therapeutic Advances in Chronic Disease

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Chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS) are functional disorders of the lower gastrointestinal tract. Their prevalence in the general population is between 5% and 20%. Both disorders are chronic, with a relapsing and remitting natural history. The medical treatment of both conditions is unsatisfactory at present, and they represent a huge burden to the health service. Linaclotide is a first-in-class minimally adsorbed, 14-amino-acid peptide agonist of guanylate cyclase C. The drug acts on the intestinal enterocyte. As a consequence of this, intestinal fluid secretion is increased and intestinal transit is accelerated. The efficacy of linaclotide has been studied in both CIC and constipation-predominant IBS (IBS-C). Randomized controlled trials consistently demonstrate that the drug is effective in the treatment of CIC and IBS-C, across a wide range of continuous and dichotomous endpoints. The number needed to treat with linaclotide to prevent one patient with CIC or IBS-C failing to respond to therapy is between 5 and 8 in studies that have reported these data. Overall, in the majority of trials, total numbers of adverse events have been no more frequent with linaclotide, but rates of diarrhoea have been consistently higher. While the drug is clearly effective in the treatment of CIC, there are other evidence-based therapies available, and head-to-head efficacy and cost-effectiveness studies are therefore required to further delineate the role of linaclotide in the treatment of the condition. In IBS-C there are no other licensed therapies available, and linaclotide therefore represents a novel treatment with great promise.

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Efficacy of Linaclotide for Patients With Chronic Constipation

Cited by 211 publications

References 24 publications

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

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

Treatment of gastrointestinal autonomic neuropathy

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

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