HERTFORDSHIRE MEDICINES MANAGEMENT COMMITTEE (HMMC)

LINACLOTIDE FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) RECOMMENDED FOR RESTRICTED USE

Name: What it is Indication Date Decision NICE / SMC Guidance generic decision last status (trade) revised Linaclotide Guanylate Symptomatic treatment of April 2014 Final NICE – New medicine (Constella ®) Cyclase-C moderate to severe (update of evidence summary 16, receptor agonist irritable bowel syndrome September April 2013, (GCCA) with constipation (IBS-C) 2013 HMMC) SMC – accepted for in adults. restricted use

HMMC Recommendation:

RECOMMENDED FOR PRESCRIBING IN PRIMARY OR SECONDARY CARE, for IBS-C, in line with agreed IBS pathway:

• Restricted to patients who have not responded adequately or cannot tolerate all other treatment options. • If there is no response to linaclotide after a trial of 4 weeks, treatment should be stopped. o Complete response is defined as >3 complete spontaneous complete bowel movements/week. o Partial response is defined as at least 1 extra spontaneous complete bowel movement/week compared to baseline. • GPs are advised not to add linaclotide to the repeat template on the clinical system until efficacy has been reviewed.

EFFICACY SAFETY • Two 6 month trials involving over 800 patients, over 12 and • No long term safety data. 26 weeks, demonstrated superiority of linaclotide over • Main side effect is diarrhoea. placebo.

COST PATIENT FACTORS • Cost/patient/year for licensed doses of linaclotide is £489.96. • None identified • In comparison, cost/patient/year of Laxido ® at a dose of 2 sachets/day is £130.06 (but higher doses may be required in treatment refractory patients).

Assessment against Ethical Framework

Evidence of Clinical Effectiveness • Two 6 month trials against placebo involving over 800 patients, over 12 and 26 weeks. • Results showed that linaclotide was superior to placebo in increasing spontaneous bowel movements and improving abdominal pain and bloating symptoms associated with IBS-C. • Comparative assessments against antispasmodics, other laxatives or antidepressants are not available. • The main side effect is diarrhoea, reported in 20% patients in trials, and persisting beyond 28 days in more than half of those reporting it. • Long term safety data is lacking.

This HMMC recommendation is based upon the evidence available at the time of publication. The recommendation will be reviewed upon request in the light of new evidence becoming available. Page 1 of 2

Cost of treatment and Cost Effectiveness

Annual Cost of IBS-C treatments

£900

£800 £776.42

£700

£600

£489.96 £500

£400 Annual cost Annual

£300

£200 £130.06 £83.75 £100 £53.48 £50.87 £50.87 £25.05 £0 Prucalopride Linaclotide Macrogols Sodium Ispaghula husk Docusate sodium Senna Bisacodyl (Resolor) (Constella) (Laxido) picosulfate (Fybogel) (Dioctyl) 15mg daily 10mg daily 2mg daily 290mcg daily 2 sachets daily (Dulcolax pico 2 sachets daily 200mg daily perles) 10mg daily Drug and dose

NB. Prucalopride is licensed for chronic constipation in women, not for IBS-C

• The estimated number of patients in each CCG who may be eligible to receive treatment with linaclotide is 2000. • If 10% (200) patients are initiated on this treatment instead macrogols, the additional annual cost pressure for each CCG’s prescribing budget would be about £65k. • If linaclotide is used instead of prucalopride in suitable patients, there will be a cost saving. • Despite identifying weaknesses in the cost-effectiveness modelling for linaclotide, the SMC judged that the economic case for linaclotide had been demonstrated.

The needs of the population The needs of the specific population with IBS-C not responding to conventional treatments may be high as there are no alternative licensed treatments options available. For male patients, prucalopride is not an option as it is only licensed for constipation in women.

The needs of the community The needs of the community may be impacted if linaclotide replaced other standard alternatives, by creating a cost pressure which may affect the ability of the local health economies to provide other services.

Equity No impact anticipated.

Policy Drivers • A local specialist has expressed an interest in using linaclotide. Specialists at two other local Trusts have been consulted and have not expressed an interest. • A neighbouring CCG, Bedfordshire has approved the use of linaclotide for IBS-C in primary and secondary care. • SMC and AWMSG has accepted linaclotide for restricted use in IBS-C, as a cost effective option after other treatments have failed.

Implementability A need for a primary care treatment pathway for IBS management has been identified and also for suitable patient support material to advise on diet and lifestyle management of the condition.

References • Linaclotide hard capsules 290micrograms (Constella), Scottish Medicines Consortium, 10 May 2013, SMC Linaclotide May 2013 • NICE Evidence Summary New Medicines 16: Irritable bowel syndrome with constipation in adults: linaclotide, 9 April 2013 ESNM16 linaclotide April 2013.jsp • NICE Clinical Guideline 61 Irritable bowel syndrome, February 2008 CG61 IBS Feb 2008.pdf • Commissioning Support linaclotide (Constella ), MTRAC, June 2013 MTRAC Linaclotide-Summary-Jun-13.pdf • All Wales Medicines Strategy Group (AWMSG), February 2014 FAR linaclotide AWMSG • NICE pathway Irritable bowel syndrome in adults, October 2012, NICE IBS pathway Oct 2012 • Irritable bowel syndrome and diet, NICE/British Dietetic Association 2008 (available on CCGs’ websites). • NICE CG 61 Irritable bowel syndrome: algorithm of IBS diagnosis and management within primary care, September 2012 NICECG61 IBS algorithm.pdf • Bedfordshire and Luton Joint Prescribing Committee (JPC) Bulletin 181: Linaclotide for moderate to severe irritable bowel syndrome with constipation http://www.gpref.bedfordshire.nhs.uk/media/97509/ADVGUID_LinaclotideIBS_Bulletin181.pdf Produced by Hertfordshire Pharmacy and Medicines Optimisation Team Hertfordshire, Bedfordshire and Luton Commissioning Support NHS Central Eastern Commissioning Support Unit This HMMC recommendation is based upon the evidence available at the time of publication. The recommendation will be reviewed upon request in the light of new evidence becoming available. Page 2 of 2