2 Research recommendations
- 2.1 Induction of remission for people with moderate ulcerative colitis: prednisolone compared with aminosalicylates
- 2.2 Induction of remission for people with moderate ulcerative colitis: prednisolone compared with beclometasone
- 2.3 Induction of remission for people with subacute ulcerative colitis that is refractory to systemic corticosteroids
- 2.4 Maintenance treatment for people with mild to moderate ulcerative colitis
- 2.5 Risk tool for predicting the likelihood of needing surgery for adults with acute severe ulcerative colitis
The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in appendix M of the full guideline.
2.1 Induction of remission for people with moderate ulcerative colitis: prednisolone compared with aminosalicylates
What is the clinical and cost effectiveness of prednisolone compared with aminosalicylates for the induction of remission for people with moderate ulcerative colitis?
Currently, people with moderate active ulcerative colitis most frequently receive either aminosalicylates or prednisolone as treatment, but there is no direct trial evidence comparing these treatments. Therefore people may receive treatment that is either less effective (in terms of symptom reduction or resolution, quality of life or healing of the colonic mucosa) or associated with greater side effects (especially with prednisolone). This is an important question in children, but the use of steroids is more contentious in children and there may be greater reluctance to use them because of possible effects on growth and development. People with moderate exacerbations of ulcerative colitis would be recruited and randomised to receive either prednisolone plus a bone-protecting agent or high-dose aminosalicylates. Primary end-points should be clinical remission and endoscopic remission.
2.2 Induction of remission for people with moderate ulcerative colitis: prednisolone compared with beclometasone
What is the clinical and cost effectiveness of prednisolone plus an aminosalicylate compared with beclometasone plus an aminosalicylate for induction of remission for people with moderate ulcerative colitis?
Evidence exists about the effectiveness of beclometasone plus an aminosalicylate for induction of remission in people with moderate ulcerative colitis. It seems likely that any corticosteroid would have a similar effect to beclometasone (in combination with an aminosalicylate), but no evidence was available to confirm this. Prednisolone is cheap and readily available. Evidence to show comparable or better clinical and cost effectiveness of prednisolone plus an aminosalicylate compared with beclometasone plus an aminosalicylate would represent a significant cost benefit and potentially increased or at least similar clinical efficacy. The research should take the form of a double-blind randomised controlled trial. The outcomes should include patient satisfaction measures.
2.3 Induction of remission for people with subacute ulcerative colitis that is refractory to systemic corticosteroids
What are the benefits, risks and cost effectiveness of methotrexate, ciclosporin, tacrolimus, adalimumab and infliximab compared with each other and with placebo for induction of remission for people with subacute ulcerative colitis that is refractory to systemic corticosteroids?
The best drug treatment for people with subacute ulcerative colitis whose condition fails to respond to treatment with oral prednisolone (a systemic corticosteroid) is unclear. Without effective treatment the condition may deteriorate, and may lead to the person requiring hospital admission for intravenous corticosteroid treatment or even surgery. It is common clinical practice to offer treatment with methotrexate or a calcineurin inhibitor (ciclosporin or tacrolimus), but high-quality evidence to guide clinicians is lacking. The use of infliximab in such cases was not recommended by NICE in technology appraisal guidance 140.This question should be investigated by a multicentre randomised, placebo-controlled trial in adults in secondary care. Outcomes should include patient-centred outcome measures.
What is the clinical and cost effectiveness of regular maintenance treatment compared with no regular treatment (but rapid standard treatment if a relapse occurs) in specific populations with mild to moderate ulcerative colitis?
Maintenance treatment reduces the chance of relapses occurring, but for much of the time a drug is being taken with no obvious benefit, and it may have side effects. An exacerbation of ulcerative colitis can usually be effectively treated or stopped if treatment is given when the first symptoms or signs of a relapse appear. It may be both clinically and cost effective to manage ulcerative colitis in this way, with people receiving episodic treatment rather than taking a drug continuously. This form of treatment may be appropriate if relatively few (for example, 1 or 2) mild relapses occur per year. The study population would be people in whom mild to moderate ulcerative colitis of any extent is in remission and who are not taking immunomodulator or biological drugs.
2.5 Risk tool for predicting the likelihood of needing surgery for adults with acute severe ulcerative colitis
To develop and validate a risk tool that predicts the likelihood of needing surgery for adults admitted to hospital with acute severe ulcerative colitis.
Acute severe ulcerative colitis is a life-threatening emergency. About 30% of people admitted to hospital with acute severe ulcerative colitis will require colectomy to avoid colonic perforation during the emergency admission. The Truelove and Witts' severity index is used to define the clinical severity of disease on admission but has not been validated as a predictor of the need for colectomy during treatment. The Travis (Oxford) criteria are used to predict the likelihood of colectomy after 3 days of treatment with intravenous steroids, but may be less useful later in the course. No tools have been developed and validated in patients receiving rescue therapy with anti-tumour necrosis factor (TNF) antibodies or ciclosporin. A validated tool that can reliably predict a person's likelihood of needing a colectomy over the course of an admission to hospital for treating acute severe ulcerative colitis would allow the medical and surgical teams and the person to prepare for colectomy and potentially inform decisions about introducing rescue therapy with ciclosporin or infliximab and when continued medical therapy is unlikely to be successful. There may also be psychological and nutritional benefits to the person and cost benefits to the NHS (for example, shorter length of inpatient stay; decreased risk of infection; less use of rescue therapy). The tool would be developed by a derivation study using a prospective cohort. The tool would be validated using a different prospective cohort from that of the derivation study.