Linaclotide: A Review of Its Use in the Treatment of Irritable Bowel Syndrome with Constipation

Linaclotide (Constella®) is a synthetic 14-amino acid peptide, structurally related to guanylin and uroguanylin, that acts as a potent guanylate cyclase C receptor agonist. It is a first-in-class agent recently approved in the EU for the treatment of adult patients with moderate to severe irritable bowel syndrome with constipation (IBS-C). Linaclotide has very low oral bioavailability and acts locally in the gastrointestinal tract to stimulate fluid secretion, increase colonic transit, and reduce abdominal pain. In phase III trials, once-daily, oral linaclotide significantly increased compared with placebo the proportions of 12-week abdominal pain/discomfort responders and 12-week degree-of-relief responders (co-primary endpoints recommended by the European Medicines Agency). Linaclotide also significantly increased the proportions of responders at 26 weeks compared with placebo, and significantly improved all abdominal symptoms and measures of bowel function at 12 weeks compared with placebo. In addition, linaclotide generally improved health-related quality of life compared with placebo. Linaclotide was generally well tolerated; the most common adverse event was diarrhoea. Thus, linaclotide is a novel and effective single agent for the treatment of IBS-C in adults.