Review article: linaclotide for the management of irritable bowel syndrome with constipation. Issue 4 (16th January 2014)

• Record Type: Journal Article
• Authors: Layer, P.; Stanghellini, V.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 39:Issue 4(2014)
• Page Start: 371
• Page End: 384
• Publication Date: 2014-01-16
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.12604
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt12604-abs-0001"> <title>Summary</title> <sec id="apt12604-sec-0001" sec-type="section"> <title>Background</title> <p>Irritable bowel syndrome with constipation (IBS‐C) represents a significant burden to patients and healthcare systems due to its prevalence and lack of successful symptomatic resolution with established treatment options. Linaclotide 290 μg has recently been approved by the European Medicines Agency (EMA) for moderate‐to‐severe IBS‐C and by the US Food and Drug Administration for IBS‐C (290 μg dose) and for chronic constipation (145 μg dose).</p> </sec> <sec id="apt12604-sec-0002" sec-type="section"> <title>Aim</title> <p>To summarise data leading to the approval of linaclotide for IBS‐C, with focus on EMA‐pre‐specified outcome measures.</p> </sec> <sec id="apt12604-sec-0003" sec-type="section"> <title>Methods</title> <p>Literature search of a peer‐review database (PubMed) and review of congress abstracts on linaclotide preclinical and clinical trial data in IBS‐C.</p> </sec> <sec id="apt12604-sec-0004" sec-type="section"> <title>Results</title> <p>Preclinical studies suggest that the guanylate cyclase C agonist (GCCA) linaclotide acts through elevation of cyclic guanosine monophosphate (cGMP) levels, leading to accelerated gastrointestinal (GI) transit through increased fluid secretion and reduced visceral hypersensitivity. Clinical trial data demonstrate that linaclotide improves abdominal symptoms (pain, bloating) and bowel symptoms (constipation) compared with placebo in patients with IBS‐C. The most frequent side effect, diarrhoea, results from the therapeutic action of linaclotide. Linaclotide acts locally in the GI tract with minimal systemic exposure, resulting in low oral bioavailability and thus a low risk of relevant systemic adverse effects.</p> </sec> <sec id="apt12604-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Linaclotide, a first‐in‐class GCCA, is a promising new drug with a novel, dual mechanism of action that, unlike more well‐established agents, can relieve the abdominal pain, bloating and constipation associated with IBS‐C and has a low propensity for systemic side effects.</p> </sec> </abstract>