Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy

2.1 Ulcerative colitis is a chronic condition in which inflammation develops in the large intestine. Its exact cause is unknown although hereditary, infectious and immunological factors have been proposed as possible causes. Symptoms vary according to the extent and severity of the disease and may include bloody diarrhoea, abdominal pain, weight loss, fatigue, anaemia and an urgent need to defaecate. Some patients may also have extra‑intestinal manifestations involving joints, eyes, skin and liver. Symptoms can flare up then disappear for months or even years, but approximately 50% of patients with ulcerative colitis will relapse at least once a year. Ulcerative colitis can cause complications such as primary sclerosing cholangitis (inflamed and damaged bile ducts), bowel cancer, osteoporosis and toxic megacolon (swelling of the colon caused by trapped gases, which can be life‑threatening).

2.2 Ulcerative colitis can develop at any age but the peak incidence is between 15 and 25 years of age with a second, smaller peak between 55 and 65 years. It is estimated that approximately 128,400 people in England have ulcerative colitis. Around 80% of the people affected have mild or moderate disease and 20% have severe disease.

2.3 The modified Truelove and Witts severity index is widely used to classify the severity of ulcerative colitis. It defines mild ulcerative colitis as fewer than 4 bowel movements daily; moderate ulcerative colitis as more than 4 daily bowel movements but the patient is not systemically ill; and severe ulcerative colitis as more than 6 bowel movements daily and the patient is also systemically ill (as shown by tachycardia, fever, anaemia or a raised erythrocyte sedimentation rate). Severe ulcerative colitis, as defined by the Truelove and Witts severity index, is potentially life threatening and normally requires hospitalisation and emergency care. This is aligned with the UK definition of 'acute severe ulcerative colitis'. NICE's guideline 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. This appraisal includes moderately to severely active ulcerative colitis but not acute severe ulcerative colitis (that is, severe ulcerative colitis according to the Truelove and Witts severity index). Recommendations for treating acute severe ulcerative colitis can be found in NICE's guideline on managing ulcerative colitis and NICE's technology appraisal guidance on infliximab for acute exacerbations of ulcerative colitis.

2.4 Treatment for ulcerative colitis aims to relieve symptoms during a flare‑up and then to maintain remission. The management of moderately to severely active ulcerative colitis involves treatment with oral or topical aminosalicylates (sulfasalazine, mesalazine, balsalazide or olsalazine), or with corticosteroids if aminosalicylates are contraindicated or not tolerated. Oral corticosteroids or drugs that affect the immune response can also be added if the disease does not respond to aminosalicylates. Colectomy is a treatment option if symptoms are inadequately controlled or if the patient has a poor quality of life on conventional therapy.