National Clinical Guideline Centre Ulcerative colitis Ulcerative colitis Management in adults, children and young people Clinical guideline Methods, evidence and recommendations June 2013 Final version Commissioned by the National Institute for Health and Care Excellence Ulcerative colitis Contents Disclaimer Healthcare professionals are expected to take NICE clinical guidelines fully into account when exercising their clinical judgement. However, the guidance does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of each patient, in consultation with the patient and/or their guardian or carer. Copyright National Clinical Guideline Centre, 2013. Funding National Institute for Health and Care Excellence National Clinical Guideline Centre, 2013. Ulcerative colitis Contents Contents Guideline development group members ................................ ................................ ...................... 12 Acknowledgments ...................................................................................................................... 13 1 Introduction ........................................................................................................................ 14 2 Development of the guideline .............................................................................................. 17 2.1 What is a NICE clinical guideline? ....................................................................................... 17 2.2 Remit ................................................................................................................................... 17 2.3 Who developed this guideline? .......................................................................................... 18 2.4 What this guideline covers .................................................................................................. 18 2.5 What this guideline does not cover .................................................................................... 19 2.6 Relationships between the guideline and other NICE guidance ......................................... 19 3 Methods .............................................................................................................................. 21 3.1 Developing the review questions and outcomes ................................................................ 21 3.2 Searching for evidence ........................................................................................................ 23 3.2.1 Clinical literature search ......................................................................................... 23 3.2.2 Health economic literature search ......................................................................... 24 3.3 Evidence of effectiveness .................................................................................................... 24 3.3.1 Inclusion/exclusion ................................................................................................. 25 3.3.2 Methods of combining clinical studies ................................................................... 26 3.3.1 Type of studies ....................................................................................................... 28 3.3.2 Type of analysis ...................................................................................................... 28 3.3.3 Appraising the quality of evidence by outcomes ................................................... 28 3.3.4 Grading the quality of clinical evidence ................................................................. 30 3.3.5 Risk of bias .............................................................................................................. 30 3.3.6 Inconsistency .......................................................................................................... 31 3.3.7 Indirectness ............................................................................................................ 31 3.3.8 Imprecision ............................................................................................................. 31 3.4 Evidence of cost-effectiveness ............................................................................................ 33 3.4.1 Literature review .................................................................................................... 33 3.4.3 Cost-effectiveness criteria ...................................................................................... 35 3.5 Developing recommendations ............................................................................................ 36 3.5.1 Research recommendations .................................................................................. 37 3.5.2 Validation process .................................................................................................. 37 3.5.3 Updating the guideline ........................................................................................... 37 3.5.4 Disclaimer ............................................................................................................... 37 3.5.5 Funding ................................................................................................................... 37 4 Guideline summary .............................................................................................................. 38 National Clinical Guideline Centre, 2013. 4 Ulcerative colitis Contents 4.1 Algorithms ................................ ................................ ................................ ........................... 38 4.2 Key priorities for implementation ....................................................................................... 41 4.3 Full list of recommendations .............................................................................................. 43 4.4 Key research recommendations ......................................................................................... 51 5 Inducing remission in people with ulcerative colitis .............................................................. 52 5.1 Clinical introduction: Pharmacological treatment .............................................................. 54 5.2 Review question: In adults, children and young people with mild to moderate ulcerative colitis, what is the clinical and cost-effectiveness of corticosteroids, aminosalicylates and immunomodulators (mercaptopurine, azathioprine, methotrexate and tacrolimus) for the induction of remission compared to themselves (different preparations and doses), each other, combinations of preparations (oral and topical) and placebo? ................................................................................................... 55 5.3 Clinical evidence: Topical aminosalicylates......................................................................... 57 5.4 Evidence profile ................................................................................................................... 59 5.4.1 Topical aminosalicylates versus placebo ................................................................ 59 5.4.2 Topical aminosalicylates versus topical aminosalicylates (preparation comparison) ........................................................................................................... 62 5.4.3 Topical aminosalicylates versus topical aminosalicylates (dose comparison) ....... 66 5.4.4 Topical aminosalicylates versus topical aminosalicylates (regimen comparison) ........................................................................................................... 70 5.4.5 Topical aminosalicylates versus topical aminosalicylates (regimen and dose comparison) ........................................................................................................... 71 5.5 Economic evidence ............................................................................................................. 72 5.6 Evidence statements ........................................................................................................... 72 5.6.1 Clinical evidence statements .................................................................................. 72 5.6.2 Economic evidence statements ............................................................................. 74 5.7 Clinical evidence: Topical corticosteroids ........................................................................... 74 5.8 Evidence profile ................................................................................................................... 75 5.8.1 Topical corticosteroids versus placebo .................................................................. 75 5.8.2 Topical corticosteroids versus topical corticosteroids (preparation comparison) ........................................................................................................... 76 5.8.3 Topical corticosteroids versus topical corticosteroids (dose comparison) ............ 77 5.8.4 Topical corticosteroids versus topical corticosteroids (interclass comparisons) ... 78 5.8.5 Topical corticosteroids versus topical corticosteroids (interclass and preparation comparison) ....................................................................................... 81 5.9 Economic evidence ............................................................................................................. 82 5.10 Evidence statements ..........................................................................................................