Sarah Cripps presents an overview of NICE Evidence Update 65 for Crohn’s disease and discusses some key points for consideration alongside current guidance
- A summary of selected new evidence relevant to NICE Clinical Guideline (CG) 152 on Crohn’s disease: management in adults, children and young people (2012)2 has recently been published:
- this summary, NICE Evidence Update 651 is intended to increase awareness of some new and relevant evidence published in the literature that suggests a change in practice and potential impact on current guidance
- The key points from NICE Evidence Update 651 are linked to the key priority areas of NICE CG1522 and should be used in conjunction with the recommendations made in NICE CG1522
- Crohn’s disease affects people of all ages and is a lifelong condition. Appropriate patient information and support remain key:
- general practitioners should be aware of contact details for colleagues within secondary care, including IBD specialist nurses and patient support groups such as Crohn’s and Colitis UK19
- Hospital admissions and biologics are among the biggest cost pressures for CCGs in the management of patients with IBD
- Prescribing of biologics should be under the care of a specialist gastroenterologist but it is important that GPs are aware of patients in their practice who are receiving these treatments. The use of biologics is likely to increase
- The range of biologics licensed for IBD is increasing and some are the subject of future NICE reviews. Because specialist gastroenterologists may wish to use these agents outside current NICE guidance, GP commissioners are likely to see an increase in Individual Funding Requests for them
- Clinical commissioning groups should participate in regular audit of patients on biologics and agree formularies and budgets with their colleagues in secondary care to ensure cost effective and appropriate use of these agents
- Shared-care policies should be in place for the prescribing of immunomodulators between primary and secondary care
- Patients on immunomodulators and/or biologics are a priority group for seasonal influenza vaccination (and pneumonococcal, human papillomavirus, hepatitis B, as per national guidelines):
- these patients should avoid any live vaccines
- The care of pregnant patients with IBD should be done conjunctively between primary and secondary care.
- treating acute attacks promptly and effectively to induce remission
- maintenance of remission
- minimising toxicity related to drug treatment
- selecting patients who will benefit from surgery and/or endoscopic treatment
- optimisation of nutrition and/or growth
- smoking cessation
- minimising psychological concerns
- management of disease complications
- maintaining or improving quality of life.
NICE Clinical Guideline 152
NICE Evidence Update 65
NICE Quality Standard for inflammatory bowel disease
- attendance at school
- work absenteeism
- unplanned hospital admissions for IBD
- length of hospital stay after surgery for IBD
- readmissions after surgery for IBD
- people with long-term conditions feeling supported to manage their condition
- patient experience of services.
Patient information and support
Induction and maintenance of remission
Biologics and biosimilars
Monitoring for osteopenia and assessing fracture risk
Conception and pregnancy
Other national guidelines
|Potential impact on guidance|
|Patient information and support|
|Parents of children with Crohn’s disease need information to help decide whether to start TNF inhibitor treatments. Parents have particular worries about the risk of cancer and lack of long-term safety data||√|
|Inducing remission in Crohn’s disease|
|Azathioprinea and mercaptopurineb may not be better than placebo for inducing remission of Crohn’s disease; however infliximab plus azathioprine may be more effective than infliximab alone||√*|
|Methotrexatec may not be effective for inducing remission in Crohn’s disease, and infliximab plus methotrexate may not be more effective than infliximab alone||√|
|There is no evidence to suggest that naltrexoned is effective for inducing remission of Crohn’s disease||√|
|Adalimumab may be an effective treatment for inducing remission of Crohn’s disease in people who previously had infliximab treatment failure.||√*|
|People taking TNF inhibitors may be at increased risk of opportunistic infections||√*|
|The presence of antibodies against TNF inhibitors is associated with loss of response to treatment and lower trough levels of the drug in blood serum||√|
|Maintaining remission in Crohn’s disease|
|Thiopurine treatment may be feasible in people who previously stopped treatment with these drugs because of adverse events. However, rare but serious adverse events, such as pancreatitis or bone marrow failure, may reoccur.||√|
|On continuing adalimumab treatment for 4 years, less than a third of people maintain remission; the same proportion of people may stop treatment because of adverse events.||√|
|Maintaining remission in Crohn’s disease after surgery|
|Adalimumab may be more effective than azathioprine or mesalazinee in maintaining remission of Crohn’s disease after surgery||√*|
|Monitoring for osteopenia and assessing fracture risk|
|Low BMI may be the most important risk factor for osteoporosis in people with Crohn’s disease||√|
|Conception and pregnancy|
|TNF inhibitors do not seem to be associated with major adverse effects when used during pregnancy, but infants exposed to these drugs in utero may be at increased risk of adverse reactions to live vaccines||√|
|Thiopurine use in pregnancy may be associated with pre-term birth, but may not be associated with low birth weight or congenital malformations||√|
Please see the full commentaries for details of the evidence informing these key points.
The section headings used in the table above are taken from NICE CG152.1
NB: Evidence Updates do not replace current NICE guidance and do not provide formal practice recommendations.
a At the time of publication of this Evidence Update, not all azathioprine products had UK marketing authorisation for this indication, please see the summary of product characteristics for each drug formulation.
b At the time of publication of this Evidence Update, mercaptopurine did not have UK marketing authorisation for this indication. Informed consent should be obtained and documented.
c At the time of publication of this Evidence Update, methotrexate did not have UK marketing authorisation for this indication. Informed consent should be obtained and documented.
d At the time of publication of this Evidence Update, naltrexone did not have UK marketing authorisation for this indication and was not considered for NICE CG152.
e At the time of publication of this Evidence Update, mesalazine did not have UK marketing authorisation for this indication. Informed consent should be obtained and documented.
* Evidence Updates are intended to increase awareness of new evidence and do not change the recommended practice as set out in current guidance. Decisions on how the new evidence may impact guidance will be made when the need to update guidance is reviewed by NICE. For further details of this evidence in the context of current guidance, please see the full commentary.
NICE. Crohn’s disease: Evidence update. Evidence Update 65. NICE, 2014. Available at: www.evidence.nhs.uk/about-evidence-services/bulletins-and-alerts/evidence-updates/evidence-updates-by-date Reproduced by kind permission.
Box 1: Other relevant national guidelines on Crohn’s disease
- British Society of Gastroenterology (BSG)
- British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN)
- The IBD Standards Group
- Standards for the healthcare of people who have inflammatory bowel disease (IBD). IBD Standards 2013 update17
- Ulcerative colitis: Management in adults, children and young people. Clinical Guideline 166. London: NICE, 201318
- The treatment of Crohn’s disease often requires specialist medications:
- CCGs need to commission services to support the use and monitoring of these agents
- Non-biologic agents can be prescribed in primary care under specialist supervision but require CCGs to commission enhanced services and shared- care protocols to ensure regular blood-testing and monitoring, which are needed for the safe use of these agents:
- these protocols should also include guidance for vaccination in patients with Crohn’s disease and who are on disease-modifying medication
- Biologic agents are usually prescribed in secondary care but are expensive:
- the costs for these drugs are excluded from the Payment by Results tariff so the cost of them falls to CCGs
- Clinical commissioning groups should therefore work with secondary care to agree formularies and ensure that these drugs are prescribed cost efficiently and in line with NICE technology appraisals (which CCGs have a legal duty to fund)
- Clinical commissioning groups may also need to identify funding panels to consider exceptional requests from specialists to fund treatments outside NICE recommendations or awaiting NICE appraisal.
- NICE. Crohn’s disease: Evidence update. Evidence Update 65. NICE, 2014. Available at: www.evidence.nhs.uk/about-evidence-services/bulletins-and-alerts/evidence-updates/evidence-updates-by-date (accessed 20 October 2014).
- NICE. Crohn’s disease: Management in adults, children and young people. Clinical Guideline 152. NICE, 2012. Available at: www.nice.org.uk/guidance/cg152 (accessed 20 October 2014).
- National Clinical Guideline Centre. Crohn’s disease. Management in adults, children and young people. Clinical Guideline 152. Methods, evidence and recommendations. London: NCGC, 2012. Available at: www.nice.org.uk/nicemedia/live/13936/61002/61002.pdf nhs_accreditation
- NICE. Inflammatory bowel disease. Quality Standard, in development. NICE, 2014. Available at: www.nice.org.uk/guidance/indevelopment/gid-qsd70/documents (accessed 20 October 2014).
- Cripps S. Support and advice in treating patients with Crohn’s disease. Guidelines in Practice; 16 (4): 10–27. Available at: bit.ly/10yoC7T (accessed 4 November 2014).
- British Medical Association and the Royal Pharmaceutical Society. British National Formulary. London, Pharmaceutical Press. Available at: www.medicinescomplete.com/about/publications.htm (accessed 20 October 2014).
- NICE. Infliximab (review) and adalimumab for the treatment of Crohn’s disease. Technology Appraisal 187. Available at: www.nice.org.uk/guidance/TA187 (accessed 21 October 2014).
- Van der Valk M, Mangen M-J, Leenders M et al. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study. Gut 2014; 63 (1): 72–79.
- NICE website. Inflammatory bowel disease. In development. www.nice.org.uk/guidance/conditions-and-diseases/digestive-tract-conditions/inflammatory-bowel-disease (accessed 4 November 2014).
- Rinaudo-Gaujous M, Paul S, Tedesco E et al. Review article: biosimilars are the next generation of drugs for liver and gastrointestinal diseases. Aliment Pharmacol Ther 2013; 38 (8): 914–924.
- Rahier J, Ben-Horin S, Chowers Y et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009; 3 (2): 47–91.
- Mowat C, Cole A, Windsor A et al. Guidelines for the management of inflammatory bowel disease in adults. BSG 2011. Available at: www.bsg.org.uk/clinical-guidelines/ibd/guidelines-for-the-management-of-inflammatory-bowel-disease.html
- NICE. Osteoporosis: assessing the risk of fragility fracture. Clinical Guideline 146. Available at: www.nice.org.uk/guidance/CG146 (accessed 20 October 2014).
- Nielsen O, Loftus E Jr, Jess T. Safety of TNF-α inhibitors during IBD pregnancy: a systematic review. BMC Medicine 2013; 11: 174.
- Personal communication. Anja St Clair Jones, 2013.
- Sandhu B, Fell J, Beattie R, Mitton S. Guidelines for the management of IBD in children in the United Kingdom. British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), 2008. Available at: www.bspghan.org.uk/guidelines
- IBD Standards Group. Standards for the healthcare of people who have inflammatory bowel disease (IBD). IBD Standards 2013 update. Available at: www.ibdstandards.org.uk
- NICE. Ulcerative colitis: Management in adults, children and young people. Clinical Guideline 166. NICE, 2013. Available at: www.www.nice.org.uk/guidance/cg166
- Crohn’s and Colitis UK. www.crohnsandcolitis.org.uk (accessed 4 November 2014).