Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C

Two product licences for a new form of interferon alfa, pegylated interferon alfa (called peginterferon alfa), have now been granted, both for use as monotherapy and for combination therapy with ribavirin in adults with hepatitis C. The pegylated form of interferon alfa contains an essentially inert 'tail', the function of which is to slow down the rate at which the body eliminates the molecule, enabling dosing to be less frequent. Of the 2 forms of pegylated interferon, peginterferon alfa-2a has a 40 kD branched chain polyethylene glycol molecule attached to the interferon with a stable bond. Peginterferon alfa-2b has a linear 12 kD polyethylene glycol chain that is attached via an unstable bond that breaks down in solution, releasing interferon alfa-2b.

Ribavirin doses for combination therapy are as follows. In conjunction with peginterferon alfa-2a (as for interferon alfa-2a), people who have HCV genotype 1 or 4 (and usually those who have genotype 5 or 6) and who weigh less than 75 kg take 1,000 mg daily of ribavirin in divided doses. People who weigh more than 75 kg take 1,200 mg ribavirin daily in divided doses. For people with HCV genotype 2 or 3 (and less usually those who have genotype 5 or 6) the dose of ribavirin is 800 mg daily in divided doses. In conjunction with peginterferon alfa-2b (as for interferon alfa-2b) and regardless of genotype, people who weigh less than 65 kg take 800 mg of ribavirin daily in divided doses, people who weigh 65 to 85 kg take 1,000 mg daily in divided doses, and people who weigh more than 85 kg take 1,200 mg daily in divided doses.

Peginterferon alfa has a much longer plasma half-life (50 to 130 hours for peginterferon alfa-2a and about 40 hours for peginterferon alfa-2b) than interferon alfa. It therefore needs to be injected only once per week, and the aggregate dose per month can be lower than for interferon, reducing most side effects. However, data show a higher incidence of neutropenia and thrombocytopenia for peginterferon alfa as either monotherapy or combination therapy than for the corresponding treatment regimen with interferon alfa. These adverse events may be managed by dose reduction.

For people who are considered for peginterferon alfa combination therapy, standard haematological tests and blood chemistry (full blood count and differential platelet count, liver function tests, uric acid, serum bilirubin, serum creatinine, and electrolyte concentrations) are necessary for all people before initiating therapy. The HCV genotype is also determined and baseline viral load established. Liver biopsy is undertaken, if there are no increased risks, in order to assess liver scarring and necro-inflammation according to an accepted severity scale. This is important in determining the need for treatment for people with significant fibrosis and necro-inflammation. People are seen weekly for 4 weeks, and then monthly during treatment, to check for side effects such as haemolysis, neutropenia, thyroid changes, depression and retinopathy.

Both peginterferon alfa-2a and alfa-2b are administered once a week by subcutaneous injection. The dose for peginterferon alfa-2a is 180 micrograms for either monotherapy or combination therapy. The dose for peginterferon alfa-2b is 1.5 micrograms per kg body weight (combination therapy), and either 0.5 micrograms or 1.0 micrograms per kg body weight (monotherapy).

Substituting peginterferon alfa for interferon alfa increases the 4-week cost of the interferon component from about £200 to about £550. Thus, a 24-week course of combination therapy with peginterferon alfa will cost about £6,000. For monotherapy, the 24-week costs for interferon alfa and peginterferon alfa are about £1,200 and £3,200, respectively. The cost of a 48-week course is double that of a 24-week course (excluding VAT, BNF 45th edition). Costs may vary in different settings because of negotiated procurement discounts.

In pregnant or breastfeeding women, treatment with peginterferon alfa is contraindicated. Treatment with ribavirin is also contraindicated for these groups. For full details of side effects and contraindications of peginterferon alfa and of ribavirin, see the Summary of Product Characteristics.