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). Relapses are more frequent if a short course of steroids is used (for example as may be used in exacerbations of asthma).

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 (2):

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 the addition 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.

Vedolizumab is recommended by NICE as an option for treating moderately to severely active Crohn's disease only if a TNF-α inhibitor has failed or a TNF-α inhibitor cannot be tolerated or is contra-indicated. (3)

Ustekinumab is recommended by NICE as an option for treating moderately to severely active Crohn's disease in patients who have failed to respond adequately to, were intolerant of or have contra-indications to conventional therapy or a TNF‑alpha inhibitor. (4)

Risankizumab is recommended by NICE as an option for previously treated moderately to severely active Crohn's disease if the disease has not responded well enough or lost response to a previous biological treatment, or a previous biological treatment was not tolerated, TNF-alpha inhibitors are not suitable.(5)

Risankizumab has a safety profile comparable to other approved biological therapies. (6)

Upadacitinib is now recommended by NICE as an option for treating moderately to severely active Crohn's disease in adults, if the disease has not responded well enough or lost response to a previous biological treatment or a previous biological treatment was not tolerated or TNF-alpha inhibitors are not suitable. (7)

Once remission has been achieved, the choice of drug for the prevention of relapse and maintenance of remission has to be carefully considered (8)

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

References:

1. Torres J, Bonovas S, Doherty G, et al. ECCO guidelines on therapeutics in Crohn's disease: medical treatment. J Crohns Colitis. 2020 Jan 1;14(1):4-22.
2. NICE. Crohn’s disease: management. NICE guideline NG129. Published May 2019
3. Vedolizumab for treating moderately to severely active Crohn's disease after prior therapy; NICE Technology Appraisal Guidance, August 2015
4. Ustekinumab for moderately to severely active Crohn’s disease after previous treatment; NICE Technology Appraisal Guidance, July 2017
5. Risankizumab for previously treated moderately to severely active Crohn's disease; NICE Technology appraisal guidance, May 2023
6. Choi D, Sheridan H, Bhat S. Risankizumab-rzaa: a new therapeutic option for the treatment of Crohn's disease. Ann Pharmacother. 2023 May;57(5):579-84.
7. Upadacitinib for previously treated moderately to severely active Crohn’s disease; NICE Technology appraisal guidance, June 2023
8. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021 Apr;160(5):1570-83.