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NICE guidance

NICE (2010) recommendations for use of biologics

When to use?

Infliximab and adalimumab are recommended as treatment options for adults with severe active Crohn’s disease or active fistulising Crohn’s disease,  whose disease has not responded to conventional therapy (including antibiotics, drainage, immunosuppressive and/or corticosteroid treatments), or who are intolerant of or have contraindications to conventional therapy.

How long to use?

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.

Should treatment be stopped at 12 months?

People should then have their disease reassessed to determine whether ongoing treatment is still clinically appropriate. 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.

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.

Which biologic to use: infliximab or adalimumab?

Treatment should normally be started with the less expensive drug (taking into account drug administration costs, required dose and product price per dose). The costs will vary depending on local arrangement

Discuss the treatment regime?

Infliximab Adalimumab
Severe Active Crohn’s disease

5-mg/kg intravenous infusion followed by another 5-mg/kg infusion 2 weeks after the first.

If a person’s disease does not respond after two doses, no additional treatment with infliximab should be given.

In people whose disease responds-maintenance treatment (another 5-mg/kg infusion at 6 weeks after the initial dose, followed by infusions every 8 weeks).

In adults, dose escalation is an option for people whose disease has stopped responding. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit after dose adjustment.

Severe Crohn’s disease (both luminal and fistulising)

80 mg via subcutaneous injection, followed by 40 mg 2 weeks later.

If there is a need for a more rapid response to therapy, a dose of 160 mg followed by 80 mg 2 weeks later can be used, though the risk of adverse events with this higher dose is greater during induction. (Higher dose in increasingly used in clinical practice)

After induction treatment the recommended dose is 40 mg every other week. This can be increased to 40 mg every week in people whose disease shows a decrease in response to treatment. Continued therapy should be carefully reconsidered in patients whose disease does not respond within 12 weeks of initiating treatment.

Fistulising disease

5-mg/kg infusion followed by additional 5-mg/kg infusions at 2 and 6 weeks after the first.

If a person’s disease does not respond after three doses, no further treatment with infliximab should be given.

In people whose disease responds, infliximab can be given as maintenance treatment (5-mg/kg infusions every 8 weeks) or as re-administration treatment (5-mg/kg when signs and symptoms recur, followed by infusions of 5-mg/kg every 8 weeks).

In adults, dose escalation is an option for people whose disease has stopped responding.

Define severe disease as discussed in NICE 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 (3–4 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.
  • The CDAI is frequently used to assess disease severity. It is a composite of overall activity of Crohn’s disease as assessed by clinicians, and has eight variables weighted according to their ability to predict disease activity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 1–7 days, and other measurements such as the patient’s weight and haematocrit. A CDAI score of less than 150 is considered to be remission, a score greater than 220 is considered to define moderate to severe disease, and a score greater than 300 is considered to be severe disease. The paediatric CDAI (PCDAI) is an instrument similar to the CDAI but with less emphasis on subjectively reported symptoms and more emphasis on laboratory parameters of intestinal inflammation.
  • The Harvey-Bradshaw Index is another commonly used tool, which correlates well with CDAI. It is based on assessments of general wellbeing, abdominal pain, number of diarrhoeal stools per day, and the presence of abdominal mass and associated complications. Patients with a score of 8 to 9 or higher are considered to have severe disease.

Discuss paediatric use of biologics?

Infliximab, within its licensed indication, is recommended for the treatment of people aged 6–17 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.

Fistulising Crohn’s disease: For people aged 6–17 years, infliximab is given as a 5-mg/kg intravenous infusion followed by additional 5-mg/kg doses at 2 and 6 weeks after the first dose, then every 8 weeks thereafter.

NICE guidance: TA187 Crohn’s disease – infliximab (review) and adalimumab (review of TA40)

http://www.nice.org.uk/nicemedia/live/12985/48552/48552.pdf


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