biological therapy in Crohns disease

Last edited 06/2019 and last reviewed 05/2022

These are genetically engineered proteins (e.g. - monoclonal antibodies) which are directed against cytokines such as tumour necrosis factor alpha (TNFalpha) which mediate the inflammation in Crohn's disease (1)

The therapeutic antibodies infliximab, adalimumab are the two licensed drugs used in this disease.

• they are administered parenterally
• usually persist in the body for many weeks with long lasting effects
• efficacy between the two drugs have shown few differences in large randomised controlled trials (1)

Indications for anti-TNF alpha therapy include

• induction of response
• induction of remission
• maintenance for patients with moderate or severely active Crohn's disease despite (or because of or intolerance of) therapy with corticosteroids and/or immunomodulators (1)

Relative or absolute contraindications to anti-TNF alpha treatment include

• sepsis
• tuberculosis
• optic neuritis (demyelination)
• infusion reaction
• cancer (1)

NICE have stated (2):

• infliximab and adalimumab 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. People should then have their disease reassessed to determine whether ongoing treatment is still clinically appropriate
  
  
• when starting infliximab or adalimumab 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
      
      
• infliximab is recommended 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
  
  
• treatment with infliximab or adalimumab 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
  
  
• infliximab, within its licensed indication, is recommended for 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
  
  
• treatment with infliximab or adalimumab should only be started and reviewed by clinicians with experience of TNF inhibitors and of managing Crohn's disease
  
  
• ustekinumab and vedolizumab
• ustekinumab or vedolizumab are options for treating moderately to severely active Crohn's disease, that is, for adults who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF-alpha inhibitor or have medical contraindications to such therapies

If a patient presents with new symptoms within two months of receiving biological therapy, an opportunistic infection should be suspected (1)

Reference:

• 1. Cummings JR, Keshav S, Travis SP. Medical management of Crohn's disease. BMJ. 2008;336(7652):1062-6
• 2. NICE (May 2019). Crohn's disease: management