Title: Filgotinib for treating moderately to severely active ulcerative colitis (ID3736)
Funder: Department of Health and Social Care

Abstract: Ulcerative colitis is the most common inflammatory bowel disease. The cause of ulcerative colitis is unknown. Hereditary, infectious and immunological factors have been proposed as possible causes. It can develop at any age, but peak incidence is between the ages of 15 and 25 years, with a second, smaller peak between 55 and 65 years. It has been estimated that around 106,000 people in England have ulcerative colitis, of whom about 52% have moderate to severe disease[1],[2]._x000D_ _x000D_ Ulcerative colitis usually affects the rectum, and a variable extent of the colonproximal to the rectum. The symptoms of ulcerative colitis include bloody diarrhoea, colicky abdominal pain, urgency, tenesmus, fatigue and anaemia. Some patients may have extra-intestinal manifestations involving joints, eyes, skin and liver. Ulcerative colitis is associated with significant morbidity; symptoms can have a debilitating impact on quality of life and daily life, including physical, social and mental wellbeing. It is a lifelong disease, and symptoms can recur or the disease can go into remission for months or even years. Around 50% of people with ulcerative colitis will have at least one relapse per year[3]. About 80% of these are mild to moderate and about 20% are severe[3]. Complications of ulcerative colitis may include haemorrhage, perforation, stricture formation, abscess formation and anorectal disease. Some people may also develop primary sclerosing cholangitis, osteoporosis and toxic megacolon. People with long-standing disease have an increased risk of bowel cancer._x000D_ _x000D_ The aim of treatment in active disease is to address symptoms of bloody diarrhoea, urgent need to defecate and abdominal pain, and thereafter to maintain remission. Initial management depends on clinical severity, extent of disease and the person’s preference, and may include aminosalicylates (sulfasalazine, mesalazine, balsalazide or olsalazine), corticosteroids (beclometasone, budesonide, hydrocortisone or prednisolone) and biologics. An immunosuppressant (such as mercaptopurine or azathioprine) may be considered to maintain remission if aminosalicylates fail to do so._x000D_ _x000D_ NICE technology appraisal 329 recommends infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis in adults whose disease has responded inadequately to conventional therapy including corticosteroids and mercaptopurine or azathioprine, or who cannot tolerate, or have medical contraindications for, such therapies. Vedolizumab (NICE technology appraisal 342) is recommended for treating moderately to severe active ulcerative colitis. Tofacitinib (NICE technology appraisal 547) is recommended for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated, or the disease has responded inadequately or lost response to treatment. NICE technology appraisal 633 recommends ustekinumab for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated, or the disease has responded inadequately or lost response to treatment, only if a tumour necrosis factor-alpha inhibitor has failed, cannot be tolerated or is not suitable._x000D_ _x000D_ For people admitted to hospital with acute severe ulcerative colitis NICE guideline [NG130] recommends offering intravenous corticosteroids to induce remission and assessing the need for surgery. Surgery may be considered as emergency treatment for severe ulcerative colitis that does not respond to drug treatment. People may also choose to have elective surgery for unresponsive or frequently relapsing disease that is affecting their quality of life. The scope of this appraisal does not include severe ulcerative colitis that is a medical emergency requiring intensive inpatient treatment._x000D_ _x000D_ References_x000D_ 1. National Institute for Health and Care Excellence (2015), Technology Appraisal 342; Costing statement [online; accessed 20 July 2020]._x000D_ 2. Office for National Statistics, Clinical commissioning group population estimates; Mid 2018 [online; accessed 20 July 2020]._x000D_ 3. National Institute for Health and Care Excellence (2014), Quality standards and indicators; Briefing Paper [online; accessed 20 July 2020].

Lay abstract: To appraise the clinical and cost effectiveness of filgotinib within its marketing authorisation for treating moderately to severely active ulcerative colitis.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL