OBJECTIVES: The aims were: firstly, to review the definition and diagnosis of irritable bowel syndrome with constipation (IBS-C, a subtype of IBS); secondly, to critically assess current therapies for IBS-C with a focus on effectiveness for abdominal pain; and thirdly, to review clinical studies evaluating the efficacy of linaclotide, a therapy recently approved by the US Food and Drug Administration for the treatment of adults with IBS-C and chronic idiopathic constipation and the European Medicines Agency for the symptomatic treatment of moderate to severe IBS-C in adults, and in development for treatment of IBS-C worldwide. METHODS: A comprehensive literature review was performed to summarize IBS-C and current treatments. MEDLINE and gastrointestinal society congress proceedings were searched to identify data from linaclotide clinical studies in adults with IBS-C published between January 2010 and August 2012. RESULTS: IBS-C patients have chronic, relapsing symptoms. Rome III diagnostic criteria define the presence of chronic abdominal pain that improves with defecation and has onset associated with changes in stool frequency or form as a key element of IBS-C and other IBS subtypes. IBS-C patients generally are not completely satisfied with existing therapies. A therapy that treats bowel and abdominal symptoms effectively and can be taken safely on a chronic basis is a current unmet need for IBS-C patients. The guanylate cyclase-C agonist linaclotide has been shown to reduce visceral hypersensitivity in preclinical studies and to improve abdominal pain and constipation symptoms in phase 2 and 3 clinical trials of IBS-C patients. CONCLUSIONS: IBS-C is a functional gastrointestinal disorder with chronic, relapsing abdominal and constipation symptoms. By virtue of its effects in relieving abdominal pain by reducing visceral hypersensitivity and improving constipation symptoms by increasing intestinal secretion and accelerating transit, linaclotide may be uniquely positioned for a role in the management of IBS-C patients.
OBJECTIVES: The aims were: firstly, to review the definition and diagnosis of irritable bowel syndrome with constipation (IBS-C, a subtype of IBS); secondly, to critically assess current therapies for IBS-C with a focus on effectiveness for abdominal pain; and thirdly, to review clinical studies evaluating the efficacy of linaclotide, a therapy recently approved by the US Food and Drug Administration for the treatment of adults with IBS-C and chronic idiopathic constipation and the European Medicines Agency for the symptomatic treatment of moderate to severe IBS-C in adults, and in development for treatment of IBS-C worldwide. METHODS: A comprehensive literature review was performed to summarize IBS-C and current treatments. MEDLINE and gastrointestinal society congress proceedings were searched to identify data from linaclotide clinical studies in adults with IBS-C published between January 2010 and August 2012. RESULTS:IBS-Cpatients have chronic, relapsing symptoms. Rome III diagnostic criteria define the presence of chronic abdominal pain that improves with defecation and has onset associated with changes in stool frequency or form as a key element of IBS-C and other IBS subtypes. IBS-Cpatients generally are not completely satisfied with existing therapies. A therapy that treats bowel and abdominal symptoms effectively and can be taken safely on a chronic basis is a current unmet need for IBS-Cpatients. The guanylate cyclase-C agonist linaclotide has been shown to reduce visceral hypersensitivity in preclinical studies and to improve abdominal pain and constipation symptoms in phase 2 and 3 clinical trials of IBS-Cpatients. CONCLUSIONS:IBS-C is a functional gastrointestinal disorder with chronic, relapsing abdominal and constipation symptoms. By virtue of its effects in relieving abdominal pain by reducing visceral hypersensitivity and improving constipation symptoms by increasing intestinal secretion and accelerating transit, linaclotide may be uniquely positioned for a role in the management of IBS-Cpatients.
Authors: Kavisha Arora; Yunjie Huang; Kyushik Mun; Sunitha Yarlagadda; Nambirajan Sundaram; Marco M Kessler; Gerhard Hannig; Caroline B Kurtz; Inmaculada Silos-Santiago; Michael Helmrath; Joseph J Palermo; John P Clancy; Kris A Steinbrecher; Anjaparavanda P Naren Journal: JCI Insight Date: 2017-10-05
Authors: Erik S Blomain; Jieru E Lin; Crystal L Kraft; Urszula T Trela; Justin M Rock; Amanda S Aing; Adam E Snook; Scott A Waldman Journal: Expert Rev Clin Pharmacol Date: 2013-08-24 Impact factor: 5.045
Authors: Gerhard Hannig; Boris Tchernychev; Caroline B Kurtz; Alexander P Bryant; Mark G Currie; Inmaculada Silos-Santiago Journal: Front Mol Neurosci Date: 2014-04-16 Impact factor: 5.639