The utilisation of linaclotide in patients with Irritable Bowel Syndrome predominantly with constipation (IBS-C) in the United Kingdom: a retrospective observational study using the Clinical Practice Research Datalink

Date of ISAC Approval: 
08/06/2018
Lay Summary: 
Irritable bowel syndrome (IBS) is a condition that affects the digestive system and causes symptoms like stomach cramps, bloating, diarrhoea and constipation. These symptoms come and go and can last up from days to months at a time. It mostly affects women between the age of 20 and 30, and in the United Kingdom is estimated to affect between 10 and 20% people. People with IBS have different symptoms, some patients mainly experience diarrhoea (IBS-D), some constipation (IBS-C) and other patients alternate between the two (IBS-M). Previous IBS treatments include lifestyle and diet improvements and medications, such as laxatives, which treat IBS-related symptoms. Linaclotide was the first medication to be approved in the European Union for moderate to severe IBS-C. This study aims to look at the types of people that are prescribed linaclotide. In particular, groups of patients who use linaclotide and have not been studied previously are of interest, including the elderly, pregnant and breastfeeding women, and patients with other conditions or medications. To provide more information on this medication, the length of time that patients use linaclotide will also be studied.
Technical Summary: 
Irritable bowel syndrome (IBS) is a chronic, relapsing gastrointestinal condition characterised by abdominal pain, bloating, and changes in bowel habits. Prevalence estimations vary with the diagnostic criteria used, and in the United Kingdom (UK) were estimated between 9.5% and 22%. IBS can be classified according to Rome III criteria on the basis of the stool's characteristics: IBS predominantly with diarrhoea (IBS-D); IBS predominantly with constipation (IBS-C); and IBS with mixed bowel habits (IBS-M), with approximately one third of IBS patients having each type. The commercialisation of linaclotide (Constella), a guanylate cyclase-C receptor agonist with visceral analgesic and secretory activities, was approved as the first medicine authorised for the symptomatic treatment of moderate-to-severe IBS-C in adults in the European Union (EU). This study plans to describe the characteristics of patients newly prescribed linaclotide, especially in certain population subgroups for which the use of linaclotide was not sufficiently documented in the clinical programme (including the elderly, males, pregnant or breast-feeding women, and patients with specific comorbidities or taking other medications), and in groups with potential off-label use and patients with potential for abuse/excessive use. Linaclotide treatment patterns will be also described.
Health Outcomes to be Measured: 
Primary Health Outcomes - Characteristics of patients prescribed linaclotide at the time of first prescription - Characteristics of patients by specific sub-groups of interest: paediatric population, elderly population patients with diabetes, hypertension, or cardiovascular disease diagnostic codes, patients with codes for constipation only - Number and percentage of patients with the potential for linaclotide off-label use as a laxative, in other types of constipation disorders and in paediatric population Secondary Health Outcomes - Proportion and characteristics of patients prescribed linaclotide who experience discontinuation and switching to drugs potentially also used by patients with IBS-C moderate to severe - Duration of linaclotide treatment until discontinuation or switching - Effect of the indication (IBS-C diagnosis versus other) on the time from initiation to discontinuation or switching
Collaborators: 

Dr Javier Cid - Chief Investigator - Evidera, Inc
Ahunna Ukah - Collaborator - Allergan, Inc
Anna Schultze - Collaborator - Evidera, Inc
Mireia Raluy Callado - Collaborator - Evidera, Inc
Nafeesa Dhalwani - Corresponding Applicant - Evidera, Inc
Robert Donaldson - Collaborator - Evidera, Inc
Ms Sophie Graham - Collaborator - Evidera, Inc

Linkages: 
Practice IMD (Standard);Pregnancy Register