Abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis

Abatacept (Orencia, Bristol‑Myers Squibb) is a fusion protein that inhibits the activation of T cells. It is administered by intravenous infusion. Abatacept in combination with methotrexate is indicated for treating moderate to severe active polyarticular juvenile idiopathic arthritis (JIA) in paediatric patients 6 years and older whose disease has responded inadequately to other disease‑modifying antirheumatic drugs (DMARDs) including at least 1 tumour necrosis factor (TNF) inhibitor. The summary of product characteristics suggests stopping abatacept if a response to treatment is not seen within 6 months.

The summary of product characteristics lists upper respiratory tract infections as the only very common (affecting 1 in 10 people or more) adverse reaction for abatacept. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Abatacept costs £302.40 for a 250 mg vial (British National Formulary for Children, accessed September 2015). The dose of abatacept depends on body weight. For children and young people who weigh less than 75 kg, the dose is 10 mg/kg. For young people weighing over 75 kg, the adult dosing regimen applies, up to a total dose of 1,000 mg per administration. Abatacept is given at 2 and 4 weeks after the initial intravenous infusion and then every 4 weeks. The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of abatacept with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.

Adalimumab (Humira, AbbVie) is an antibody that inhibits TNF. It is administered by subcutaneous injection. Adalimumab in combination with methotrexate (or as monotherapy if methotrexate is not tolerated or is inappropriate) is indicated for:

• treating active polyarticular JIA in patients 2 years and older whose disease has responded inadequately to 1 or more DMARDs

• treating active enthesitis‑related arthritis in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy.
  
  The summary of product characteristics suggests stopping adalimumab if a response to treatment is not seen within 12 weeks.

The summary of product characteristics lists the following very common (affecting 1 in 10 people or more) adverse reactions for adalimumab: respiratory tract infections, low white blood cell count, low red blood cell count, increased blood levels of lipids, headache, abdominal pain, nausea and vomiting, rash, musculoskeletal pain, injection site reactions and increased plasma levels of liver enzymes. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Adalimumab costs £352.14 for a 40 mg prefilled pen or prefilled syringe and for a 40 mg/0.8 ml vial (British National Formulary for Children, accessed September 2015). The dose of adalimumab depends on body surface area. For children younger than 13 years, the dose is 24 mg/m2, up to a maximum single dose of 20 mg in children aged 2 to 4 years and 40 mg in children aged 4 to 12 years. It is given every other week. For young people 13 years and older, the dose is 40 mg every other week regardless of body surface area. Costs may vary in different settings because of negotiated procurement discounts.

Etanercept (Enbrel, Pfizer) is a human tumour necrosis factor receptor p75 Fc fusion protein that inhibits TNF. It is administered by subcutaneous injection. It is indicated for:

• treating polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in children and young people 2 years and older whose disease has responded inadequately to, or who cannot tolerate, methotrexate

• treating psoriatic arthritis in young people 12 years and older whose disease has responded inadequately to, or who cannot tolerate, methotrexate

• treating enthesitis‑related arthritis in young people 12 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy.
  
  The summary of product characteristics suggests stopping etanercept if a response to treatment is not seen within 12 weeks.

The summary of product characteristics lists the following very common (affecting 1 in 10 people or more) adverse reactions for etanercept: injection site reactions, upper respiratory tract infections, and bladder and skin infections. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Etanercept costs £35.75 for a 10 mg vial and £89.38 for a 25 mg vial (British National Formulary for Children, accessed September 2015). The dose of etanercept is either 0.4 mg/kg given twice weekly up to a maximum of 25 mg per dose or 0.8 mg/kg given once weekly up to a maximum of 50 mg per dose. Costs may vary in different settings because of negotiated procurement discounts.

Tocilizumab (RoActemra, Roche) is an antibody that inhibits the action of interleukin‑6. It is administered by intravenous infusion. Tocilizumab in combination with methotrexate (or as monotherapy if methotrexate is not tolerated or is inappropriate) is indicated for:

• treating juvenile idiopathic polyarthritis (rheumatoid factor positive or negative, and extended oligoarthritis) in patients 2 years and older whose disease has responded inadequately to methotrexate

• treating active systemic JIA in patients 2 years and older whose disease has responded inadequately to previous therapy with non‑steroidal anti‑inflammatory drugs and systemic corticosteroids.
  
  The summary of product characteristics suggests stopping tocilizumab if a response to treatment is not seen within 12 weeks.

The summary of product characteristics lists the following adverse reactions affecting 5 people in 100 or more for tocilizumab: upper respiratory tract infections, nasopharyngitis, headache, hypertension and abnormal liver function tests. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Tocilizumab costs £102.40 for an 80 mg vial, £256.00 for a 200 mg vial and £512.00 for a 400 mg vial (British National Formulary for Children, accessed September 2015). The dose of tocilizumab is 8 mg/kg once every 4 weeks in patients weighing 30 kg or more or 10 mg/kg once every 4 weeks in patients weighing less than 30 kg. The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of tocilizumab with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.