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inducing remission in Crohn's disease

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Corticosteroids are effective in inducing remission in Crohn’s disease but is ineffective at maintaining remission (1)

Acute severe exacerbations are treated with intravenous hydrocortisone:

  • for example, 100 mg hydrocortisone iv 8 hourly for two days

The intravenous steroids are replaced by oral prednisolone and patients are weaned off steroids as symptoms allow. The side-effects of steroids do not permit their use as a maintenance treatment. In less severe exacerbations then oral steroids may be used from the onset of management.

Prescribing regimens are not standardised, but a starting dose of 40 mg per day reducing to zero over 5 weeks, taken in addition to a 5-ASA agent, is a reasonable reflection of common practice in the use of oral steroids in inducing remission in Crohn's disease (and ulcerative colitis) (2). Relapses are more frequent if a short course of steroids is used (for example as may be used in exacerbations of asthma) (2).

Oral modified release budesonide may offer good luminal anti-inflammatory effects with reduced systemic absorption.

With respect to inducing remission in Crohn's disease NICE state (3):

Inducing remission in Crohn's disease

  • monotherapy

    • monotherapy with a conventional glucocorticoid (prednisolone, methylprednisolone or intravenous hydrocortisone) should be considered to induce remission in people with a first presentation or a single inflammatory exacerbation of Crohn's disease in a 12-month period

    • consider enteral nutrition as an alternative to conventional glucocorticoid to induce remission for:
      • children in whom there is concern about growth or side effects, and
      • young people in whom there is concern about growth

    • budesonide * should be considered for a first presentation or single inflammatory exacerbation in a 12-month period for people:
        • who have one or more of distal ileal, ileocaecal or right-sided colonic disease, AND
        • if conventional glucocorticoids are contraindicated, or if the person declines or cannot tolerate them
      • explain that budesonide is less effective than a conventional glucocorticoid, but may have fewer side effects

    • consider aminosalicylate ** treatment
      • for a first presentation or single inflammatory exacerbation in a 12-month period if conventional glucocorticoids are contraindicated, or if the person declines or cannot tolerate them
        • explain that aminosalicylates are less effective than a conventional glucocorticoid or budesonide but may have fewer side effects than a conventional glucocorticoid

    • do not offer budesonide or aminosalicylate treatment for severe presentations or exacerbations

    • do not offer azathioprine, mercaptopurine or methotrexate as monotherapy to induce remission


  • in some instances more than a single therapy will be required to induce remission (termed 'add-on' treatment)
    • add-on treatment in Crohn's disease (3):

      • azathioprine or mercaptopurine should be considered as an add-on to a conventional glucocorticosteroid or budesonide to induce remission of Crohn's disease if:
        • there are two or more inflammatory exacerbations in a 12-month period,
        • or the glucocorticosteroid dose cannot be tapered

        • thiopurine methyltransferase (TPMT) activity should assessed before offering azathioprine or mercaptopurine
          • do not offer azathioprine or mercaptopurine if TPMT activity is deficient (very low or absent). Consider azathioprine or mercaptopurine at a lower dose if TPMT activity is below normal but not deficient (according to local laboratory reference values)

      • methotrexate
        • consider addtion of methotrexate to a conventional glucocorticosteroid or budesonide to induce remission in people who cannot tolerate azathioprine or mercaptopurine, or in whom TPMT activity is deficient, if:
          • there are two or more inflammatory exacerbations in a 12-month period, or
          • the glucocorticosteroid dose cannot be tapered

      • Infliximab and adalimumab
        • infliximab and adalimumab, within their licensed indications, are recommended as treatment options for adults with severe active Crohn's disease 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
          • severe active Crohn's disease
            • defined as very poor general health and one or more symptoms such as weight loss, fever, severe abdominal pain and usually frequent (3-4 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.

     

Key:

* although use is common in UK clinical practice, budesonide is not specifically licensed for children and young people

** although use is common in UK clinical practice, mesalazine, olsalazine and balsalazide are not licensed for this indication

Reference:

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