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.