Steroids plus steroid sparing agents in 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:

• (1) Dignass A et al. The second European evidence-based consensus on the diagnosis and management of Crohn's disease: Current management. Journal of Crohn's and Colitis 2010; 4:28-62
• (2) Prescriber (2001); 12 (20): 43-58.
• (3) NICE (May 2019). Crohn's disease Management in adults, children and young people