Title: Darvadstrocel for treating complex perianal fistula in Crohn's disease [ID960]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of darvadstrocel within its marketing authorisation for treating perianal fistula in Crohn’s disease.

Lay abstract: Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract (gut) that may affect any part of the gut from the mouth to the anus. People with Crohn’s disease have acute exacerbations (‘flares’) in between periods of remission or less active disease. These flares may affect any part of the gut and are defined by location (terminal ileal, colonic, ileocolic, upper gastrointestinal), or by the pattern of the disease (inflammatory, fistulising, or stricturing). Luminal Crohn’s disease affects the lining of the intestine. Inflammation of the gut can lead to tissue damage and ulceration. A complication of such tissue damage is the development of fistula. A perianal fistula is an abnormal connection that develops between the bowel and the skin near the anus. The symptoms of perianal fistula include skin irritation around the anus, pain, passing of blood or pus when having a bowel movement and leakage of faecal matter. Fistulas are described as simple or complex depending on the location and whether there is a singular fistula tract or interlinking connections. There are currently at least 115,000 people in the UK with Crohn’s disease.(I) The incidence of Crohn’s disease is greatest in people aged between 16 and 30 years. However, it may affect people of any age. Approximately 20% of people with Crohn’s disease will develop a perianal fistula, and 30% of these people have recurrent fistulas.(1) Treatments for perianal fistula aim to treat and drain the underlying infection and heal the fistula. Medications for treating fistulas can include antibiotics, immunosuppressants (such as azathioprine or mercaptopurine) or biological treatments (such as infliximab and adalimumab). For some people surgery is needed. Following drainage of the infection, types of surgery may include use of a seton (in which a piece of thread is passed through the fistula and tied in a loop); fistulotomy (involving surgically opening the tract to allow the tissues to heal from the inside out); advancement flap procedures (attachment of a piece of rectal or anal tissue over the internal opening of the fistula following fistulotomy) or use of biosynthetic plugs to block the internal opening of the fistula. Fibrin glue is a non-surgical option for treating an anal fistula. The glue is injected into the fistula to seal the tract. NICE guidance is available for some, but not all, current treatments for perianal fistula. NICE technology appraisal 187 recommends the anti-tumour necrosis factor (TNF) inhibitors infliximab and adalimumab as treatment options for adults with severe active Crohn’s disease whose disease has not responded to conventional therapy (including immunosuppressive and/or corticosteroid treatments), or who are intolerant of or have contraindications to conventional therapy. Technology appraisal guidance 187 further recommends infliximab as a treatment option for people with active fistulising Crohn’s disease whose disease has not responded to conventional therapy (including antibiotics, drainage and immunosuppressive treatments), or who are intolerant of or have contraindications to conventional therapy. Interventional procedures guidance 410 recommends that there are no major safety concerns with using a suturable biosynthetic plug to block the internal opening of the fistula. However, data on the efficacy of this procedure is limited and the guidance states that the procedure should only be used with special arrangements for clinical governance, consent and audit or research. References 1. Gecse K, Bemelman W, Kamm M et al (2014) A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut 63:1381-1392

Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: ORAL AND GASTROINTESTINAL