3 The technologies

3 The technologies

3.1 Adalimumab (Humira, AbbVie), golimumab (Simponi, Merck Sharp & Dohme) and infliximab (Remicade, Merck Sharp & Dohme; Inflectra, Hospira; Remsima, Celltrion) are monoclonal antibodies that inhibit the pro‑inflammatory cytokine, TNF‑alpha. All 3 have the same marketing authorisation in the UK for the 'treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies'. Infliximab is also indicated for the 'treatment of severely active ulcerative colitis, in children and adolescents aged 6 to 17 years, who have had an inadequate response to conventional therapy including corticosteroids and mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies'.

Adalimumab

3.2 Adalimumab is administered by subcutaneous injection. The recommended induction dose regimen is 160 mg at week 0 and 80 mg at week 2. After induction treatment, the recommended dose is 40 mg every other week. The summary of product characteristics recommends that therapy should be stopped in patients whose disease failed to respond to adalimumab within 2 to 8 weeks after starting treatment.

3.3 The summary of product characteristics includes the following adverse reactions for adalimumab: infections (such as nasopharyngitis, upper respiratory tract infection and sinusitis), injection site reactions (including erythema, itching, haemorrhage, pain or swelling), headache, musculoskeletal pain, hepatitis B reactivation, various malignancies and serious haematological, neurological and autoimmune reactions. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.4 The price of adalimumab is £352.14 for a pre‑filled 40 mg pen or syringe, or a 40 mg/0.8 ml vial (excluding VAT; 'British National Formulary' [BNF] edition 67). Assuming the recommended dosage for adalimumab is followed (see section 3.2), the cost of adalimumab induction therapy is £2113; the cost of 4 weeks of adalimumab maintenance therapy is £704. Costs may vary in different settings because of negotiated procurement discounts.

Golimumab

3.5 Golimumab is administered by subcutaneous injection. The dose regimen of golimumab depends on the patient's body weight. For patients with a body weight of less than 80 kg, golimumab is licensed at an initial dose of 200 mg, followed by 100 mg at week 2, and then 50 mg every 4 weeks. For patients with a body weight of 80 kg or more, it is licensed at an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks. The summary of product characteristics recommends that continued golimumab therapy should be reconsidered in patients who do not benefit within 12–14 weeks after starting treatment (that is, after 4 doses).

3.6 The summary of product characteristics includes the following adverse reactions for golimumab: upper respiratory tract infection and other serious infections (including sepsis, pneumonia, tuberculosis, and invasive fungal and opportunistic infections), demyelinating disorders, lymphoma, hepatitis B reactivation, congestive heart failure, autoimmune processes (lupus‑like syndrome) and haematologic reactions. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.7 The price of golimumab is £762.97 for a pre‑filled 50 mg pen or syringe and £1525.94 for a 100 mg pre‑filled pen (excluding VAT; BNF edition 67). Merck Sharp & Dohme has agreed a patient access scheme with the Department of Health. This will make the 100 mg dose of golimumab available to the NHS at the same cost as the 50 mg dose. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. Including the patient access scheme and assuming that the recommended dosage for golimumab is followed (see section 3.5), the cost of golimumab induction therapy is £2289; the cost of 4 weeks of golimumab maintenance therapy is £763.

Infliximab

3.8 Infliximab is administered by intravenous infusion. For both the adult and paediatric populations, the recommended dose of infliximab is 5 mg/kg at weeks 0, 2 and 6, then at every 8 weeks. The summary of product characteristics recommends that continued infliximab therapy should be carefully reconsidered in adults who do not benefit within the first 14 weeks of treatment. It also states that available data do not support further infliximab therapy in children and young people aged 6 to 17 years whose disease does not respond within the first 8 weeks of treatment.

3.9 The summary of product characteristics includes the following adverse reactions for infliximab: upper respiratory tract infection, hepatitis B reactivation, congestive heart failure, serious infections (including sepsis, opportunistic infections and tuberculosis), serum sickness (delayed hypersensitivity reactions), haematologic reactions, systemic lupus erythematosus/lupus‑like syndrome, demyelinating disorders, hepatobiliary events, lymphoma, hepatosplenic T‑cell lymphoma, and serious infusion reactions. For full details of adverse reactions and contraindications, see the summary of product characteristics.

3.10 The price of infliximab is £419.62 for a 100 mg vial containing powder for reconstitution (excluding VAT; BNF edition 67). Assuming the patient weighs 77 kg and the recommended dose for infliximab is followed (see section 3.8), the cost of infliximab induction therapy is £5035; the cost of 4 weeks of infliximab maintenance therapy is £839. Costs may vary in different settings because of negotiated procurement discounts.

3.11 Biosimilar versions of infliximab (Inflectra, Hospira; Remsima, Celltrion) have a marketing authorisation in the UK for the same indications. The therapeutic indications, dosage and method of administration for Remsima and Inflectra are identical to those for the reference product (Remicade). Adverse reactions are also similar. Neither Inflectra nor Remsima had an approved list price in the UK at the time of the appraisal.

  • National Institute for Health and Care Excellence (NICE)