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Overview

  • This guideline covers the management of Crohn’s disease in children, young people and adults. It aims to reduce people’s symptoms and maintain or improve their quality of life

  • This guideline replaces CG152

  • This guideline is the basis of QS81.

Contents not included in this summary

1.1 Providing information and support

1.4 Maintaining remission in Crohn’s disease after surgery

1.5 Surgery

1.2 Inducing remission in Crohn’s disease

Monotherapy

1.2.1 Offer monotherapy with a conventional glucocorticosteroid (prednisolone, methylprednisolone or intravenous hydrocortisone) to induce remission in people with a first presentation or a single inflammatory exacerbation of Crohn’s disease in a 12-month period. [2012]

1.2.2 Consider enteral nutrition as an alternative to a conventional glucocorticosteroid to induce remission for:

  • children in whom there is concern about growth or side effects
  • young people in whom there is concern abouth growth. [2012]

1.2.3 Consider budesonide[A] for a first presentation or a single inflammatory exacerbation in a 12-month period for people:

  • who have one or more of distal ileal, ileocaecal or right-sided colonic disease[B] and
  • if conventional glucocorticosteroids are contraindicated, or if the person declines or cannot tolerate them.

Explain that  budesonide is less effective than a conventional glucocorticosteroid, but may have fewer side effects. [2012]

1.2.4 Consider aminosalicylate treatment[C] for a first presentation or a single inflammatory exacerbation in a 12-month period if conventional glucocorticosteroids are contraindicated, or if the person declines or cannot tolerate them. Explain that aminosalicylates are less effective than a conventional glucocorticosteroid or budesonide but may have fewer side effects than a conventional glucocorticosteroid. [2012]

1.2.5 Do not offer budesonide or aminosalicylate treatment for severe presentations or exacerbations. [2012]

1.2.6 Do not offer azathioprine, mercaptopurine or methotrexate as monotherapy to induce remission. [2012]

Add-on treatment 

1.2.7 Consider adding azathioprine or mercaptopurine[D] to a conventional glucocorticosteroid or budesonide[A] to induce remission of Crohn’s disease if:

  • there are 2 or more inflammatory exacerbations in a 12-months period or
  • the glucocorticosteroid dose cannot be tapered. [2012]

1.2.8 Assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine. Do not offer azathioprine or mercaptopurine if TPMT activity is deficient (very low or absent). Consider azathioprine or mercaptopurine[D] at a lower dose if TPMT activity is below normal but not deficient (according to local laboratory reference values). [2012]

1.2.9 Consider adding methotrexate[E],[F] to a conventional glucocorticosteroid or budesonide[A] to induce remission in people who cannot tolerate azathioprine or mercaptopurine, or in whom TPMT activity is deficient, if:

  • there are 2 or more inflammatory exacerbations in a 12-month period or
  • the glucocorticosteroid dose cannot be tapered. [2012]

1.2.10 Monitor the effects of azathioprine, mercaptopurine[D] and methotrexate[E],[F] as advised in the British national formulary (BNF) or British national formulary for children (BNFC)[G]. Monitor for neutropenia in people taking azathioprine or mercaptopurine even if they have normal TPMT activity. [2012]

1.2.11 Ensure that there are documented local safety monitoring policies and procedures (including audit) for people receiving treatment that needs monitoring. Nominate a member of staff to act on abnormal results and communicate with GPs, people with Crohn’s disease and their family members or carers (as appropriate). [2012]

Infliximab and adalimumab

The recommendations in the following section (1.2.12, 1.2.13, and 1.2.15 to 1.2.20) are from the NICE technology appraisal guidance on infliximab and adalimumab for the treatment of Crohn’s disease.

1.2.12 Infliximab and adalimumab, within their licensed indications, are recommended as treatment options for adults with severe active Crohn’s disease (see recommendation 1.2.18) whose disease has not responded to conventional therapy (including immunosuppressive and/or corticosteroid treatments), or who are intolerant of or have contraindications to conventional therapy. Infliximab or adalimumab should be given as a planned course of treatment until treatment failure (including the need for surgery), or until 12 months after the start of treatment, whichever is shorter. People should then have their disease reassessed (see recommendation 1.2.16) to determine whether ongoing treatment is still clinically appropriate. [2010]

1.2.13 Treatment as described in recommendation 1.2.12 should normally be started with the less expensive drug (taking into account drug administration costs, required dose and product price per dose). This may need to be varied for individuals because of differences in the method of administration and treatment schedules. [2010]

1.2.14 When a person with Crohn’s disease is starting infliximab or adalimumab (in line with recommendations 1.2.12, 1.2.15, 1.2.17 and 1.2.20), discuss options of:

  • monotherapy with one of these drugs or
  • combined therapy (either infliximab or adalimumab, combined with an immunosuppressant).

Tell the person there is uncertainty about the comparative effectiveness and long-term adverse effects of monotherapy and combined therapy. [2016]

1.2.15 Infliximab, within its licensed indication, is recommended as a treatment option for people with active fistulising Crohn’s disease whose disease has not responded to conventional therapy (including antibiotics, drainage and immunosuppressive treatments), or who are intolerant of or have contraindications to conventional therapy. Infliximab should be given as a planned course of treatment until treatment failure (including the need for surgery) or until 12 months after the start of treatment, whichever is shorter. People should then have their disease reassessed (see recommendation 1.2.16) to determine whether ongoing treatment is still clinically appropriate. [2010]

1.2.16 Treatment with infliximab or adalimumab (see recommendations 1.2.12 and 1.2.15) should only be continued if there is clear evidence of ongoing active disease as determined by clinical symptoms, biological markers and investigation, including endoscopy if necessary. Specialists should discuss the risks and benefits of continued treatment with patients and consider a trial withdrawal from treatment for all patients who are in stable clinical remission. People who continue treatment with infliximab or adalimumab should have their disease reassessed at least every 12 months to determine whether ongoing treatment is still clinically appropriate. People whose disease relapses after treatment is stopped should have the option to start treatment again. [2010]

1.2.17 Infliximab, within its licensed indication, is recommended for the treatment of people aged 6 to 17 years with severe active Crohn’s disease whose disease has not responded to conventional therapy (including corticosteroids, immunomodulators and primary nutrition therapy), or who are intolerant of or have contraindications to conventional therapy. The need to continue treatment should be reviewed at least every 12 months. [2010]

1.2.18 For the purposes of this guidance, severe active Crohn’s disease is defined as very poor general health and one or more symptoms such as weight loss, fever, severe abdominal pain and usually frequent (3 to 4 or more) diarrhoeal stools daily. People with severe active Crohn’s disease may or may not develop new fistulae or have extra-intestinal manifestations of the disease. This clinical definition normally, but not exclusively, corresponds to a Crohn’s Disease Activity Index (CDAI) score of 300 or more, or a Harvey-Bradshaw score of 8 to 9 or above. [2010]

1.2.19 When using the CDAI and Harvey-Bradshaw Index, healthcare professionals should take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the scores and make any adjustments they consider appropriate. [2010]

1.2.20 Treatment with infliximab or adalimumab should only be started and reviewed by clinicians with experience of TNF inhibitors and of managing Crohn’s disease. [2010]

Ustekinumab and vedolizumab

1.2.21 For guidance on using ustekinumab, see the NICE technology appraisal guidance on ustekinumab for moderately to severely active Crohn’s disease after previous treatment. [2019]

1.2.22 For guidance on using vedolizumab, see the NICE technology appraisal guidance on vedolizumab for treating moderately to severely active Crohn’s disease after prior therapy. [2019]

1.3 Maintaining remission in Crohn’s disease

1.3.1 Discuss with people with Crohn’s disease and their family members or carers (as appropriate) options for managing their disease when they are in remission, including both no treatment and treatment. The discussion should include the risk of inflammatory exacerbations (with and without drug treatment) and the potential side effects of drug treatment. Record the person’s views in their notes. [2012]

1.3.2 Offer colonoscopic surveillance in line with the NICE guideline on colorectal cancer prevention: colonoscopic surveillance in adults with ulcerative colitis, Crohn’s disease or adenomas. [2012]

Follow-up during remission for people who choose not to have maintenance treatment

1.3.3 When people choose not to receive maintenance treatment: 

  • discuss and agree with them and their family members or carers (as appropriate) plans for follow-up, including the frequency of follow-up and who they should see
  • ensure  they know which symptoms may suggest a relapse and should prompt a consultation with their healthcare professional (most frequently, unintended weight loss, abdominal pain, diarrhoea, general ill-health)
  • ensure they know how to access the healthcare system if they experience a relapse
  • discuss the importance of not smoking. [2012]

Maintenance treatment for people who choose this option

1.3.4 Offer azathioprine or mercaptopurine[D] as monotherapy to maintain remission when previously used with a conventional glucocorticosteroid or budesonide to induce remission. [2012]

1.3.5 Consider azathioprine or mercaptopurine[D] to maintain remission in people who have not previously received these drugs (particularly people with adverse prognostic factors such as early age of onset, perianal disease, glucocorticosteroid use at presentation and severe presentations). [2012]

1.3.6 Consider methotrexate[E],[F] to maintain remission only in people who:

  • need methotrexate to induce remission or
  • have tried but did not tolerate azathioprine or mercaptopurine for maintenance or
  • have contraindications to azathioprine or mercaptopurine (for example, deficient thiopurine methyltransferase [TPMT] activity or previous episodes of pancreatitis). [2012]

1.3.7 Do not offer a conventional glucocorticosteroid or budesonide to maintain remission. [2012]

See recommendations 1.2.10 and 1.2.11 for guidance on monitoring the effects of azathioprine, mercaptopurine and methotrexate.

See recommendation 1.2.16 for when to continue infliximab or adalimumab during remission.

1.6 Monitoring for osteopenia and assessing fracture risk

Refer to the NICE guideline on osteoporosis: assessing the risk of fragility fracture for recommendations on assessing the risk of fragility fracture in adults. Crohn’s disease is a cause of secondary osteoporosis.

1.6.1 Do not routinely monitor for changes in bone mineral density in children and young people. [2012]

1.6.2 Consider monitoring for changes in bone mineral density in children and young people with risk factors, such as low body mass index (BMI), low trauma fracture or continued or repeated glucocorticosteroid use. [2012]

1.7 Conception and pregnancy

1.7.1 Give information about the possible effects of Crohn’s disease on pregnancy, including the potential risks and benefits of medical treatment and the possible effects of Crohn’s disease on fertility. [2012]

1.7.2 Ensure effective communication and information‑sharing across specialties (for example, primary care, obstetrics and gastroenterology) in the care of pregnant women with Crohn’s disease. [2012]

Footnotes

[A] Although use is common in UK clinical practice, at the time of publication (May 2019), budesonide did not have a UK marketing authorisation specifically for children and young people. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[B] See recommendations 1.5.1 and 1.5.2 for when to consider surgery early in the course of the disease for people whose disease is limited to the distal ileum.

[C] Although use is common in UK clinical practice, at the time of publication (May 2019) mesalazine, olsalazine and balsalazide did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[D] Although use is common in UK clinical practice, at the time of publication (May 2019) mercaptopurine and most preparations of azathioprine did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[E] Although use is common in UK clinical practice, at the time of publication (May 2019) not all formulations of methotrexate have a UK marketing authorisation for this indication, and the licensed formulations only have a UK marketing authorisation for adults. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[F] Follow BNF/BNFC cautions on prescribing methotrexate.

[G] Advice on monitoring of immunosuppressives can be found in the BNF/BNFC. The monographs for individual drugs should be consulted.

© NICE 2019. Crohn’s disease: management.  Available from: www.nice.org.uk/guidance/ng129. All rights reserved. Subject to Notice of rights.

NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.

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