3 The technologies
3.1 Peginterferon alfa‑2a (Pegasys, Roche Products) in combination with ribavirin has a UK marketing authorisation for the treatment of children and adolescents 5 years of age and older with chronic hepatitis C, who test positive for serum hepatitis C virus (HCV) ribonucleic acid (RNA) and who have not previously received any treatment. Peginterferon alfa‑2a is administered subcutaneously once weekly. The dose depends on body surface area, and it should not be used in children with a body surface area of less than 0.71 m2 (for whom there are no data). The recommended treatment duration is 24 weeks (genotypes 2 or 3) or 48 weeks (all other genotypes) depending on baseline viral load and whether or not a child has a virological response (defined as a 100‑fold decrease in, or undetectable levels of, serum HCV RNA) at week 24. Virological response by week 24 is predictive of sustained virological response. If adverse reactions occur, the dose can be reduced.
3.2 Peginterferon alfa‑2b (ViraferonPeg, Merck Sharp and Dohme [MSD]) in combination with ribavirin has a UK marketing authorisation for the treatment of children aged 3 years and older and adolescents who have chronic hepatitis C without hepatic decompensation, who test positive for serum HCV RNA and who have not previously received any treatment. Dosing of peginterferon alfa‑2b for children and adolescents is determined by body surface area and the recommended dose is 60 micrograms/m2 per week subcutaneously in combination with ribavirin. The recommended treatment duration is 48 weeks for children and adolescents with genotype 1 or 4. Treatment should be stopped after 12 weeks if serum HCV RNA decreases less than 100‑fold compared with pre-treatment levels or if serum HCV RNA is detectable at week 24. For children and adolescents with genotype 2 or 3, treatment is 24 weeks. If adverse reactions occur, the dose can be reduced.
3.3 Ribavirin (manufactured as Copegus by Roche Products) has a marketing authorisation in combination with peginterferon alfa‑2a or interferon alfa‑2a for treating chronic hepatitis C; the marketing authorisation for Copegus does not include specific recommendations for use in children and young people. Copegus is available as 200‑mg or 400‑mg tablets. Ribavirin manufactured by MSD (as Rebetol) has a marketing authorisation in combination with peginterferon alfa‑2b or interferon alfa‑2b for treating chronic hepatitis C in children and young people aged 3 years and older. Rebetol is available as an oral solution and 200‑mg hard capsules. The recommended dose of either ribavirin in combination with peginterferon alfa‑2a or ‑2b is based on body weight; the average daily dose is 15 mg/kg, given in 2 doses. The most common adverse reactions to ribavirin include anaemia, dry cough and rash.
3.4 Peginterferon alfa‑2a and ‑2b are contraindicated for treating chronic hepatitis C in children and young people with a history of severe psychiatric conditions. The summaries of product characteristics for peginterferon alfa‑2a and ‑2b mention the following adverse reactions in children and young people: severe psychiatric and central nervous system effects (particularly depression, suicidal ideation and attempted suicide), weight loss and growth inhibition. The summaries of product characteristics state that, when deciding not to defer treatment until adulthood, it is important for clinicians to consider that combination therapy may inhibit growth and that it is uncertain whether this effect is reversible. Therefore the summaries of product characteristics suggest that a child or young person is treated before or after the pubertal growth spurt whenever possible. For full details of adverse reactions and contraindications, see the summaries of product characteristics.
3.5 The price of peginterferon alfa‑2a is £107.76 for a 135‑microgram prefilled syringe or pen and £124.40 for a 180‑microgram prefilled syringe or pen (excluding VAT; 'British national formulary' [BNF] edition 65). The price of peginterferon alfa‑2b is £1.33 per microgram and it is available in 50-, 80-, 100-, 120- and 150‑microgram pens costing £66.46, £106.34, £132.92, £159.51 and £199.38 respectively (BNF edition 65). The Assessment Group calculated that, based on an average age of 11 years, a body weight of 35.5 kg and a body surface area of 1.19 m2, a 24‑week course of peginterferon alfa‑2a plus ribavirin costs approximately £3700 and a 48‑week course of treatment costs approximately £7400; a 24‑week course of peginterferon alfa‑2b plus ribavirin oral solution costs approximately £4000 and a 48‑week course of treatment costs approximately £8100. Costs may vary in different settings because of negotiated procurement discounts.