Sarah Cripps explains how patient information and support are key priorities for implementation in ulcerative colitis and will aid induction of remission
NICE Clinical Guideline 166 on Ulcerative colitis: management in adults, children and young people has been awarded the NICE Accreditation Mark.
This Mark identifies the most robustly produced guidance available. See evidence.nhs.uk/accreditation for further details.
Ulcerative colitis is the most common type of inflammatory disease of the bowel, affecting around 146,000 people in the UK. The other common type of inflammatory bowel disease is Crohn’s disease, which has an incidence of around 115,000 people in the UK.1-3 Ulcerative colitis is a chronic, lifelong condition that is associated with significant morbidity and can affect a person’s social and psychological wellbeing, particularly if symptoms are poorly controlled.
Medical treatment with corticosteroids and immunomodulators can cause secondary health problems such as infection, and surgical treatment (colectomy) will result in a permanent end ileostomy or ileo-anal pouch. Both surgical options can be associated with complications.4
The cause of ulcerative colitis is unknown, although genetic predisposition is an important factor.1-5 Former smokers are at the highest risk of developing the disease while smokers have the least risk; however, the reason for this is unclear.5 Extra-intestinal complications affect up to 35% of patients and commonly occur in the joints, skin, bone, eyes, and the biliary tree.5
Need for the guideline
NICE Clinical Guideline (CG) 166 on Ulcerative colitis: management in adults, children and young people (see www.nice.org.uk/guidance/CG166) 1 was published in June 2013 in response to wide variations in UK practice in the management of patients with ulcerative colitis. The aim of the guideline was to standardise and improve quality of care and treatment. The guidance followed publication of NICE CG152 on the management of Crohn’s disease in October 2012 (see www.nice.org.uk/guidance/CG152). 3 Both guidelines:1,3
- are the first evidence-based clinical and cost-effective guidelines for the management of inflammatory bowel disease in the UK
- cover the care of adults, children, and young people
- are relevant to both primary and secondary care.
The main differences between Crohn’s disease and ulcerative colitis are summarised in Table 1. 1-6
This article aims to raise awareness of the NICE guideline on ulcerative colitis and to highlight key:
- principles of care
- areas for implementation
- responsibilities for primary care.
|Ulcerative colitis||Crohn's disease|
|NB breastfeeding and appendicectomy is protective||NB breastfeeding and appendicectomy is protective|
|Symptoms of active disease|
|Diarrhoea||Very common||Fairly common|
|Rectal bleeding||Very common||Fairly common|
|Weight loss||Fairly common||Common|
|Signs of malnutrition||Fairly common||Common|
|Electrolyte disturbances, iron deficiency anaemia, raised CRP/ESR, hypoaluminaemia||Common||Common|
|Pattern of disease||Both characterised by unpredictable periods of remission and relapse|
|Fissures, fistulae, and strictures||Absent||Common|
|CRP=C-reactive protein; ESR=erythrocyte sedimentation rate|
Diagnosis and assessment
Ulcerative colitis, like Crohn’s disease, can occur at any age but tends to peak between 15 and 25 years of age, with a second, smaller peak between 55 and 65 years. Both conditions are characterised by unpredictable periods of acute exacerbation or active disease (also known as a flare), interspersed with periods of remission.1-3 About 50% of people with ulcerative colitis experience a relapse at least once a year.4
Ulcerative colitis usually affects the rectum and colon, unlike Crohn’s disease where inflammation can affect the entire gastrointestinal tract.1,3 The extent of ulcerative colitis is determined by the area of inflamed colon (proximal extension). Inflammation of the rectum is known as proctitis, and inflammation of the rectum and sigmoid colon as proctosigmoiditis. Left-sided disease involves the colon distal to the splenic flexure. When the whole colon is affected, it is referred to as pan-colitis.1-3
The classic symptoms of active ulcerative colitis are:1,2
- bloody diarrhoea
- an urgent need to pass stools
- abdominal pain.
Severity of ulcerative colitis
In NICE CG166, the severity of disease is defined as ‘mild’, ‘moderate’, or ‘severe’. These categories are based on Truelove and Witts’ severity index for adults (see CG166, Table 1, at publications.nice.org.uk/ulcerative-colitis-cg166/recommendations), and the Paediatric Ulcerative Colitis Activity Index (PUCAI) for children (see CG166, Table 2, at publications.nice.org.uk/ulcerative-colitis-cg166/recommendations).1,2 Sub-acute ulcerative colitis is defined as ‘moderately to severely active ulcerative colitis that would normally be managed in an outpatient setting and does not require hospitalisation or the consideration of urgent surgical intervention’.1,2,4,5
Scope of the guideline
The scope of NICE CG166 was limited by the extent of the processes and methodology applied, and by time factors. Recommendations were based on priority areas, and the evidence reviewed covered:1,2
- patient information, education, and support for people with ulcerative colitis and their families and carers
- drug therapy for the induction of remission for mild, moderate, and acute severe disease, and maintenance of remission
- indications and timing of surgical management
- management during pregnancy
- monitoring of bone health, growth, and pubertal development in children and young people
- research recommendations.
The recommendations for each of the priority areas were made based on a systematic review of the evidence, including critical appraisal, meta-analysis, and cost-effective modelling. Where evidence was lacking, the recommendations were based on a consensus experience of good practice within the guideline development group (GDG).
Patient information and support
Patient information and support were highlighted as key priorities for implementation in induction of remission management. Ulcerative colitis, associated symptoms, treatment options, and monitoring should be discussed at every opportunity with the person (and/or their parents or carers, if appropriate) and within the multidisciplinary team. The principles of patient experience in adult NHS services (see NICE CG138 on patient experience at www.nice.org.uk/cg138) should be applied.7
The possible nature, frequency, and severity of side-effects arising from drug treatment should be discussed. The person should also be given information about their risk of developing colorectal cancer and about colonoscopic surveillance.1
Individuals are likely to receive several different treatments during the course of their illness, because of drug intolerance or a lack of response. Certain people (e.g. females, those newly diagnosed, or those using rectal products) may require more tailored information and support about their condition or treatment. It is reported that around 10% of hospital inpatients report a lack of information about treatment side-effects on discharge from hospital.1
Information about surgery
Provision of information supporting decisions about surgery is also a key priority for implementation, both for clinicians and for people facing the possibility of surgical treatment. Information should include recognition of adverse prognostic factors for people admitted with severe acute colitis, to enable timely decisions for escalating medical therapy or predicting the need for surgery. It is also important that relevant information is available to support people considering elective surgery. Support and information should also be available for post-operative care and follow up.1
Sources of published patient information
Leaflets on the disease, treatments, insurance, employment, and pregnancy have been prepared by the national group, Crohn’s and Colitis UK.8 General practitioners should have contact details of their local inflammatory bowel disease (IBD) nurse specialist, if available. As with any condition, patients should be warned about unreliable information sources.
A summary of the guideline available for the public can be accessed at publications.nice.org.uk/ulcerative-colitis-ifp166.9 All NHS and voluntary sector organisations can also use this text in their own information about ulcerative colitis, to aid implementation of the guideline.
Treatment of ulcerative colitis
Current available treatment of ulcerative colitis is directed at:1-6
- treating acute attacks promptly and effectively to induce remission
- maintenance of remission
- minimising toxicity related to drug treatment
- identifying patients who require surgery due to failure of medical therapy (30% will ultimately require colectomy for ulcerative colitis)
- optimisation of nutrition and/or growth
- minimising psychological concerns
- management of disease complications
- maintaining or improving quality of life.
Induction and maintenance of remission
Box 1: Ulcerative colitis: induction of remission*2
Mild to moderate ulcerative colitis
Proctitis or proctosigmoiditis
- offer topical aminosalicylate (enema/suppository) or
- consider adding an oral aminosalicylate (combination more efficacious) or
- consider oral aminosalicylate alone.
If aminosalicylate is declined/not tolerated/contraindicated:
- consider topical corticosteroid or oral prednisolone.
Left-sided and extensive ulcerative colitis
- offer high induction dose of oral aminosalicylate
- consider adding topical aminosalicylate or beclometasone dipropionate.
If aminosalicylate is declined/not tolerated/contraindicated or there are clinical features of sub-acute ulcerative colitis:
- offer oral prednisolone.
- infliximab (refer to NICE TA14012).
If no improvement after 4 weeks of starting step 1, move to step 2.
All extents of disease
- consider adding oral prednisolone to aminosalicylate. Stop beclometasone diproprionate, if used.
If patient is resistant to prednisolone and/or thiopurine (naive):
- consider adding oral tacrolimus to oral prednisolone (treatment usually up to 3 months).
Acute severe UC: all extents of disease—first presentation or inflammatory exacerbation
- Management should involve a gastroenterologist and colorectal surgeon.
If the patient is a pregnant woman, an obstetric and gynaecology team should also be included.
- offer IV corticosteroids AND assess likelihood need for surgery.
If no improvement, OR deterioration after 72 hours of IV corticosteroids, OR IV corticosteroids not tolerated, OR IV corticosteroids contraindicated:
- consider adding ciclosporin, or consider surgery
- consider adding infliximab if ciclosporin is contraindicated or is inappropriate (refer to NICE TA16313).
*For further information, see Algorithms 1 and 2 in the full guideline at: www.nice.org.uk/guidance/CG166/Guidance/pdf/English
Drug therapy is often required for many years and patient preference, acceptability, and potential side-effects affect not only choice, but will also impact on medication adherence. A therapeutic strategy and consistency in the management of patients with ulcerative colitis is needed, which this guideline aims to achieve.
Corticosteroids, aminosalicylates, and immunomodulators (azathioprine, mercaptopurine, ciclosporin, and tacrolimus) form the mainstay of drug treatment in NICE CG166.1 Some of these drugs can be given orally and/or topically (into the rectum). In acute severe disease, intravenous administration may be required to maximise drug absorption, and in such cases the individual will require hospital admission. Drug choice and route of administration depends on the site, extent, and severity of disease, whether it is induction or maintenance of remission, and consideration of the individual’s treatment history.1-4 Maintenance treatment is recommended for all patients and it is important that this treatment is continued during periods of remission.4
In mild to moderate ulcerative colitis, the guideline recommends the use of rectally administered topical preparations of aminosalicylate and corticosteroids (see Box 1 and Box 2).1 Topical preparations come in the form of suppositories, foam, or liquid enemas. They have reduced systemic absorption and fewer side-effects compared with oral preparations. The choice of formulation depends on the site of inflammation (e.g. suppositories are used for proctitis), consideration of the presentation, patient acceptability, preference, and cost. Patient education is essential to ensure adherence to, and benefit of, the therapy. People with poor dexterity may find using rectal products difficult and these preparations may therefore be poorly tolerated and so have limited advantage.
Enemas or suppositories should be administered just before bedtime with the individual in a supine position (i.e. lying on their back) as this allows a much longer retention time. Liquid enemas can be warmed in warm water for a few minutes, and should be inserted with the person lying in the left lateral position.
Aminosalicylates are used to induce and maintain remission in ulcerative colitis. Mesalazine (or 5-aminosalicylic acid [5-ASA]) is delivered to the gut lumen by a variety of oral and topical formulations. Modification of the delivery system for 5-ASA can increase the stability and/or alter the site of release of active drug in oral formulations.
Choice of preparation
Initial choice of preparation should take into consideration the dose frequency, cost, availability, and patient preference. The delivery characteristics of oral mesalazine preparations may vary and the British National Formulary (BNF) advises that preparations should not be considered interchangeable. They should be prescribed by brand name and not by generic name.10
For maintenance of remission, CG166 recommends that a once-daily dosing regimen should be considered, based on evidence that it can be more effective than multiple dosing and may even be superior.1,2,4,5 However, once-daily 5-ASA dosing regimens may result in more side-effects.1 It should be noted that not all oral aminosalicylates currently have a UK licence for once-daily dosing and therefore the prescriber should follow relevant professional guidance and take full responsibility for the decision. Informed consent should be obtained and documented.10
Renal function should be monitored before starting an oral aminosalicylate, at 3 months of treatment, and then annually during treatment (more frequently in renal impairment). Blood disorders can also occur and patients should be advised to report any unexplained:10
- sore throat
The oral aminosalicylate should be stopped if there is a suspicion of blood dyscrasias.10
Oral prednisolone and beclometasone are recommended in NICE CG166 for induction of remission, as shown in Box 1.1 For acute severe disease requiring hospital admission, intravenous hydrocortisone is necessary. Beclametasone diproprionate is licensed only as an adjunct therapy with aminosalicylates for a maximum duration of 4 weeks. Rectal corticosteroids are recommended for use in mild-to-moderate proctitis/sigmoiditis, but are not as effective as rectal aminosalicylates.1,4 Corticosteroids have no role in the maintenance of remission.1,2,4,5 All patients taking corticosteroids must be issued with a steroid card.10
Ciclosporin and tacrolimus are used to induce remission, depending on the severity of the disease and the patient’s response to other treatments. The use of methotrexate in the treatment of ulcerative colitis, although common in practice, is not recommended by NICE because of lack of evidence.2 Azathioprine and mercaptopurine are recommended in NICE CG166 for the maintenance of remission in ulcerative colitis (see Box 2).1
Biologic agents, such as the tumour necrosis factor (TNF)-alpha inhibitors (infliximab and adalimumab), are both licensed for severe, active disease. They should only be started and reviewed by clinicians with experience of using TNF inhibitors and managing ulcerative colitis. The use of infliximab in severe, active disease is covered in separate NICE technology appraisals (TA140 and TA163; see www.nice.org.uk/TA140 and www.nice.org.uk/TA163),11,12 which approve its use for induction of remission in severe, active disease.
Adalimumab is not currently approved by NICE for the treatment of ulcerative colitis, either in severe, active disease, or for maintenance of remission, despite having a UK licence.13
NICE is due to review and publish guidance on the use of infliximab, adalimumab, and golimumab for the treatment of moderately to severely active ulcerative colitis after failure of conventional therapy (including a review of TA140 and TA262)11,13 in early 2015.14 A separate technology appraisal on the use of vedolizumab (an ?4 ?7 integrin antagonist) in treating severely active ulcerative colitis has also been proposed.15 The management of biologic agents is expected to remain under the care of an experienced inflammatory bowel disease gastroenterologist.
Box 2: Ulcerative colitis: maintenance of remisssion*
Mild to moderate proctitis/proctosigmoiditis
- consider topical aminosalicylate (enema/suppository) and/or low-dose oral aminosalicylate (combination more efficacious).
Left-sided and extensive ulcerative colitis
- offer low dose of oral aminosalicylate.†?‡
If two or more exacerbations occur within 12 months that require systemic corticosteroids, OR remission is not maintained with aminosalicylate:
- consider azathioprine or mercaptopurine.
After a single episode of acute severe ulcerative colitis:
- consider azathioprine or mercaptopurine
- consider low dose 5-ASA (if azathioprine/mercaptopurine is contraindicated or not tolerated).
* For further information, see Algorithms 1 and 2 in the full guideline at: www.nice.org.uk/guidance/CG166/Guidance/pdf/English
† consider patient preference, side-effects, and cost when choosing aminosalicylate
‡ once daily aminosalicylate
Notes for prescribers
Unlicensed use of drugs
Healthcare professionals should be aware that, although commonly adopted as part of accepted practice in the UK, the use of many of the drugs recommended in NICE CG166 for ulcerative colitis (e.g. the immunomodulators [azathioprine, mercaptopurine, ciclosporin, tacrolimus]) was outside their UK marketing authorisation at the time of publication of the guideline. Many of the drugs do not have a UK licence for use in children, including some oral and topical aminosalicylates. Reference should be made to the British National Formulary (BNF) and the British National Formulary for Children (BNFC), as appropriate. Informed consent for the use of these drugs should be obtained and documented, and the prescriber must take full responsibility for their use.1,2,10 See also ‘Shared care protocols’, below.
Drug dosages are not specified in NICE CG166, but Box 3 provides a guide to typical dose ranges.2,4-6,10,16
Thiopurine methyltransferase monitoring
Thiopurine methyltransferase (TPMT) activity should be assessed before initiating azathioprine or mercaptopurine because of the risk of neutropenia in patients where TPMT activity is deficient (very low or absent). Lower treatment doses can be considered if TPMT activity is below normal but not deficient.3
Drug levels for ciclosporin and tacrolimus
Trough drug levels (i.e. levels of the drug before a dose) should be monitored (by blood testing) for tacrolimus and ciclosporin as specified in local shared-care protocols. Target levels for these two drugs are as follows:5
- ciclosporin: within the range of 200–400 ng/ml
- tacrolimus: within the range of
- 10–15 ng/ml.
It takes 2–3 days to reach steady state after dose changes with ciclosporin and tacrimolus. Ciclosporin and tacrolimus should be prescribed by brand, because of variations in absorption between different brands.10
Box 3: Drug dose ranges for treatment of ulcerative colitis
- Oral azathioprine 2.0–2.5 mg/kg daily10
- Oral mercaptopurine 1.0–1.5 mg/kg daily10
- Oral prednisolone 40 mg each morning for 7 days, 30 mg each morning for 7 days, 20 mg each morning for 28 days, then reduce the daily dose by 5 mg each week*
- Oral beclometasone dipropionate 5 mg each morning in conjunction with aminosalicytes; maximum duration 4 weeks10
- Oral tacrolimus 0.1 mg/kg/day in two divided doses (brand specific)10
- Oral ciclosporin 2.5 mg/kg twice daily (brand specific)10
- Oral high-dose 5-ASA : follow the BNF for each drug.10
* Personal communication: Protocol for prednisolone dose reduction in the treatment of acute exacerbation of inflammatory bowel disease, Gastroenterology Unit, Oxford University Hospitals NHS Trust, 2012.
Shared-care policies between primary care doctors, gastroenterologists, and patients form a key recommendation of CG166. Patients and primary care practitioners may require additional reassurance, as several of the treatments used routinely in the management of ulcerative colitis (e.g. immunomodulators [see above]), are currently unlicensed for this indication in the UK. Immunomodulators should only be initiated by or on the advice of a specialist gastroenterologist. Biologic agents should only be initiated by secondary care specialists.1,10 It is essential that patients who are receiving aminosalicylates, immunomodulators, or biologic agents receive regular blood monitoring to ensure that they avoid any toxicity associated with these drugs.10 The effects of drugs should be monitored as advised in the current online version of the BNF or BNFC (see bnf.org). Documented local safety monitoring policies and procedures (including audit) for people receiving drugs that need monitoring is strongly recommended.
Shared-care policies should clearly highlight the responsibilities of primary and secondary care, and the person with ulcerative colitis or their parent/carer, as appropriate. A member of staff within the multidisciplinary team should be nominated to act on abnormal results and to communicate with GPs/secondary care and people with ulcerative colitis and/or their parent or carer, as appropriate.1
The role of primary care
In practice, complex cases and patients prescribed biologic agents are generally managed in secondary care whereas those in remission (on or off medication) are managed in primary care. Situations when GPs should refer patients to secondary care include:
- failure to respond to oral treatment for acute exacerbations
- toxicity to immunomodulators.
It is essential that GPs recognise the signs of an acute severe exacerbation (as defined by Truelove and Witts’ severity index and the PUCAI criteria),1 and patients are promptly referred to hospital for intensive treatment.
Care should be taken with the use of anti-motility (e.g. codeine and loperamide), and antispasmodic drugs, as they can precipitate a paralytic ileus and toxic megacolon in active disease.10
General practitioner responsibilities within a shared-care protocol for immunomodulators could include:
- prescribing immunomodulators once the dose of immunomodulators is stable. The first month of treatment is generally prescribed under secondary care
- advising the hospital consultant/specialist IBD nurse of any clinical deteriorations and monitoring for adverse effects as appropriate
- checking bloods weekly for the first month, then every 2–3 months
- providing vaccinations (i.e. seasonal influenza, pneumococcal polysaccharide vaccine, human papillomavirus according to national guidance, hepatitis B for selected patients); live vaccines should be avoided.
Surgery may be considered as emergency treatment for acute severe ulcerative colitis that is unresponsive to drug treatment. Some people may also choose to have elective surgery for unresponsive or frequently relapsing disease that is affecting their quality of life.1,2 As mentioned previously, information regarding surgery for both these patient groups (i.e. emergency and elective) is essential. Specific information regarding the care and management of stomas should be provided by a specialist, and GPs should have contact details for these experts when seeking advice.
General practitioners should be aware when initiating new medication in patients with stomas that not all drug formulations are appropriate, because of factors such as unpredictable absorption, irritation around the stoma site, and electrolyte and fluid imbalances.
Ulcerative colitis affects young adults so it is important to consider the implications regarding pregnancy. There is no evidence that ulcerative colitis or the medication recommended in NICE CG166 affects fertility in women. There is some evidence that sulfasalazine (and possibly infliximab) can affect fertility in men, but many of these effects are reversible.4 Active ulcerative colitis is more of a risk to a normal pregnancy than medication, and disease control before conception and throughout the pregnancy is associated with the best outcome for mother and baby. Higher doses of folate supplements (5 mg) are advised for patients taking sulfasalazine, as this drug interferes with folate absorption.10
NICE CG166 highlights the importance of effective communication and information-sharing across specialities (including primary care, gastroenterology, and obstetric services) in the care of pregnant women with ulcerative colitis. Pregnant women should be provided with information and the opportunity to discuss the potential risks and benefits of medical treatment to induce and maintain remission (including the possibility of admission for an acute severe inflammatory exacerbation), and of taking no treatment.1,2
General practitioners should refer to NICE CG146 for recommendations on assessing the risk of fragility fracture in adults with ulcerative colitis.17 Monitoring of bone health should be considered for children and young people with ulcerative colitits:1,2
- during chronic active disease
- after a course of systemic corticosteroids
- after recurrent active disease.
Monitoring growth and pubertal development in children and young people
The monitoring of growth and pubertal development can be carried out in a range of settings (for example, at routine appointments, acute admissions, urgent appointments in primary care, via community services, or in secondary care). NICE CG166 describes the parameters that should be monitored, the reference tools that should be used, and the frequency of monitoring. It also highlights when GPs should consider referral to secondary care. It is essential that relevant information regarding the monitoring of growth and pubertal development and disease activity is shared across relevant services.1,2
A costing report is available (via www.nice.org.uk/guidance/CG166) highlighting the resource impact of implementing NICE CG166 in England.18
The report focuses on the recommendations considered to have the greatest financial impact when implemented, or those that could generate the biggest savings. The five recommendations are:
- using a high-induction dose of an oral aminosalicylate and adding oral beclometasone dipropionate to induce remission in adults
- adding oral beclometasone dipropionate to an oral aminosalicylate to induce remission in children and young people
- adding oral tacrolimus to oral prednisolone to induce remission
- using oral mercaptopurine to maintain remission
- monitoring bone health in children and young people.
A costing template is available to support the costing report, which can be used to estimate the local cost of the implementation.
The report estimates that the annual cost of implementing the above five recommendations in a population of 100,000 people would be around £12,300.18
For clinical commissioning groups, the biggest economic pressures will continue to be hospital care and biologic agents—the use of these drugs is likely to increase. Biologic agents currently remain within the control of local commissioning groups and are excluded from the Payment by Results tariff. Owing to cost pressures, these agents are likely to require closer scrutiny on the part of CCGs and secondary care practitioners, to ensure compliance with NICE guidance, and review of individual funding requests.
The care of people diagnosed with ulcerative colitis requires a multidisciplinary team approach across primary and secondary care. NICE CG166 aims to improve the consistency and quality of care for patients with this condition. It is important that GPs are familiar with the recommendations when reviewing patients who have ulcerative colitis, particularly as many people are not routinely followed up by secondary care, and they are prescribed medication that requires close monitoring.
- NICE. Ulcerative colitis: management in adults, children and young people. Clinical Guideline 166. London: NICE, 2013. Available at www.nice.org.uk/CG166
- National Clinical Guideline Centre. Ulcerative colitis. Management in adults, children and young people. Methods evidence and recommendations. London: National Clinical Guideline Centre, June 2013. Available at: www.nice.org.uk/nicemedia/live/14189/64218/64218.pdf
- NICE. The management of Crohn’s disease in adults, children and young people. Clinical Guideline 152. London: NICE, 2013. Available at: www.nice.org.uk/CG152
- Mowat C, Cole A, Windsor A et al. Guidelines on the management of inflammatory bowel disease in adults. Gut 2011; 60 (5): 571–607.
- Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: special situations. European Crohn’s & Colitis Organisation (ECCO) guidelines, 2012 edition. Available at: download.journals.elsevierhealth.com/pdfs/journals/1873-9946/PIIS1873994609001056.pdf
- Cripps S. Support and advice in treating people with Crohn’s disease. Guidelines in Practice 2013; 16 (4): 10–27.
- NICE. Patient experience in adult NHS services: improving the experience of care for people using adult NHS services. Clinical Guideline 138. NICE, 2012. Available at: www.nice.org.uk/cg138.
- Crohn’s and Colitis UK website. www.nacc.org.uk (accessed 17 September 2013).
- NICE website. Information for the public. Ulcerative colitis. publications.nice.org.uk/ulcerative-colitis-ifp166 (accessed 25 September 2013).
- British National Formulary. www.bnf.org/bnf/index.htm (accessed 17 September 2013).
- NICE. Infliximab for subacute manifestations of ulcerative colitis. Technology Appraisal 140. London: NICE, 2008. Available at: www.nice.org.uk/TA140
- NICE. Infliximab for acute exacerbations of ulcerative colitis. Technology Appraisal 163. London: NICE, 2008. Available at: www.nice.org.uk/TA163
- NICE. Adalimumab for the treatment of moderate to severe ulcerative colitis (terminated appraisal). Technology Appraisal 262. London: NICE, 2008. Available at: www.nice.org.uk/TA262
- NICE website. Ulcerative colitis (moderate, severe)—infliximab (review TA140), adalimumab (review TA262) & golimumab (2nd line) [ID695]. www.nice.org.uk/guidance/TAG/357 (accessed 30 September 2013).
- NICE website. Proposed technology appraisals. www.nice.org.uk/ourguidance/niceguidancebytype/technologyappraisals/proposedappraisals/nowave.jsp (accessed 30 September 2013).
- Personal communication: protocol for prednisolone dose reduction in the treatment of acute exacerbation of inflammatory bowel disease. Gastroenterology Unit, Oxford University Hospitals NHS Trust, 2012.
- NICE. Osteoporosis: assessing the risk of fragility fracture. Clinical Guideline 146. London: NICE, 2012. Available at: www.nice.org/uk/cg146
- NICE. Ulcerative colitis: management in adults, children and young people—costing report. Clinical Guideline 166. London: NICE, 2013. Available at www.nice.org.uk/CG166