3 The technologies

3 The technologies

Infliximab

3.1 Infliximab (Schering-Plough Ltd) is a chimeric human–murine monoclonal antibody that binds with high affinity to TNF-α and inhibits its functional activity. Infliximab has a UK marketing authorisation for the treatment of:

  • severe, active Crohn's disease in people whose disease has not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant, or who are intolerant to or have medical contraindications for such therapies

  • fistulising, active Crohn's disease in people whose disease has not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy)

  • severe, active Crohn's disease in people aged 6–17 years whose disease has not responded to conventional therapy, including a corticosteroid, an immunomodulator and primary nutrition therapy, or who are intolerant to or have contraindications for such therapies.

3.2 The most common adverse events reported during infliximab therapy include acute infusion-related reactions, infections and delayed hypersensitivity reactions. Infliximab is contraindicated in people with moderate or severe heart failure and active infections. Before treatment is started, people must be screened for active and inactive tuberculosis. The summary of product characteristics (SPC) specifies a number of uncommon but serious adverse events related to the immunomodulatory activity. For full details of side effects and contraindications, see the SPC.

3.3 For severe, active Crohn's disease, infliximab is given as a 5-mg/kg intravenous infusion over a 2-hour period 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, infliximab regimens include maintenance treatment (another 5-mg/kg infusion at 6 weeks after the initial dose, followed by infusions every 8 weeks) or re-administration, otherwise known as episodic treatment (an infusion of 5-mg/kg if signs and symptoms of the disease recur) in line with the marketing authorisation. In adults, dose escalation is an option for people whose disease has stopped responding. According to the SPC, continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit after dose adjustment.

3.4 For fistulising, active Crohn's disease, infliximab is given as a 5-mg/kg infusion over a 2-hour period 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.

3.5 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.

3.6 A 100-mg vial of infliximab costs £419.62 (excluding VAT; 'British national formulary' [BNF], 58th edition). The drug cost differs between individuals because the dose is adjusted to each person's body weight. For example, if it is assumed that vials are not shared between patients, for a person weighing 73 kg the cost per infusion would be £1678, corresponding to four 100-mg vials needed for a dose of 365 mg. For a course of two infusions, with an assumed drug administration cost for each infusion of £258, the total cost is approximately £3872. The total cost of continuing therapy at a standard dosage for 12 months is approximately £12,584. Costs may also vary in different settings because of negotiated procurement discounts.

Adalimumab

3.7 Adalimumab (Abbott Laboratories) is a recombinant human monoclonal antibody that binds specifically to TNF-α, blocking interaction with its cell-surface receptors and thereby limiting the promotion of inflammatory pathways. Adalimumab is indicated for the treatment of severe, active Crohn's disease in people whose disease has not responded despite full and adequate treatment with an immunosuppressant and/or corticosteroid, or who are intolerant to or have contraindications to such therapies. For induction therapy adalimumab should be given in combination with corticosteroids. Adalimumab can be given as monotherapy if a person is intolerant to corticosteroids or when continued treatment with corticosteroids is inappropriate.

3.8 Common adverse events associated with adalimumab include injection site reactions and infections. Before therapy is started, all patients must be screened for active and inactive tuberculosis. Adalimumab is contraindicated in patients with moderate to severe heart failure, active tuberculosis and other severe infections. For full details of side effects and contraindications, see the SPC.

3.9 The adalimumab induction treatment dose regimen for adults with severe Crohn's disease is 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. 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. According to the SPC, continued therapy should be carefully reconsidered in patients whose disease does not respond within 12 weeks of initiating treatment.

3.10 Adalimumab costs £357.50 per 40-mg prefilled syringe (excluding VAT; BNF, 58th edition). Normal induction treatment costs approximately £1073 and the cost to continue treatment at a standard dosage for 1 year is £9295. Costs may vary in different settings because of negotiated procurement discounts.

  • National Institute for Health and Care Excellence (NICE)