Title: Tofacitinib for moderate to severely active ulcerative colitis [ID1218]
Funder: Department of Health and Social Care

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

Lay 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 146,000 people in England have ulcerative colitis, of whom about 52% have moderate to severe disease. Ulcerative colitis usually affects the rectum, and a variable extent of the colon proximal to the rectum. The symptoms of ulcerative colitis are bloody diarrhoea, colicky abdominal pain, urgency and tenesmus. Some patients may have extra-intestinal manifestations involving joints, eyes, skin and liver. Ulcerative colitis is a lifelong disease that is associated with significant morbidity; symptoms can relapse and then go into remission for months or even years. Around 50% of people with ulcerative colitis will have at least one relapse per year. About 80% of these are mild to moderate and about 20% are severe. Complications of ulcerative colitis may include haemorrhage, perforation, stricture formation, abscess formation and anorectal disease. People with long-standing disease have an increased risk of bowel cancer. The severity of ulcerative colitis may be classified based on criteria such as the Mayo Scoring System. It has 4 components: stool frequency, rectal bleeding, findings at endoscopy (typically sigmoidoscopy), and a physician's global assessment. It ranges from 0 to 12, with higher scores indicating more severe disease. A Mayo score of 6 to 12 defines moderate to severely active ulcerative colitis. It can be used for both initial evaluation and monitoring treatment response. Remission of the disease is defined by a total Mayo score of 2 points or lower, with no individual sub-score exceeding one.(1) NICE clinical guideline 166 on ulcerative colitis equates 'subacute ulcerative colitis' to moderately to severely active ulcerative colitis, which would normally be managed in an outpatient setting and does not require hospitalisation or the consideration of urgent surgical intervention. The scope of this appraisal does not include severe ulcerative colitis that is a medical emergency requiring intensive inpatient treatment. The aim of treatment in active disease is to address symptoms of urgency, frequency and rectal bleeding, and thereafter to maintain remission. NICE recommendations for managing moderately to severely active ulcerative colitis are found in NICE clinical guideline 166. Initial management depends on clinical severity, extent of disease and the person’s preference, and may include corticosteroids, or topical or oral aminosalicylates (sulfasalazine, mesalazine, balsalazide or olsalazine). If the disease does not adequately respond to oral corticosteroids (beclometasone, budesonide, hydrocortisone or prednisolone) then an immunosuppressant (such as mercaptopurine or azathioprine) may be considered. 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. NICE technology appraisal 342 recommends vedolizumab for treating moderately to severely active ulcerative colitis. Colectomy (with the creation of either an ileostomy or an ileo-anal pouch) is a treatment option for some patients, to improve the quality of life in chronic or treatment-refractory active disease or to treat cancer or pre-cancerous changes. References 1 Rutgeerts P, Sandborn W J, Feagan B G et al. (2005) Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 353:2462–2476.

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