Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C

Peginterferon alfa-2a (Pegasys, Roche Products) has a UK marketing authorisation for 'the treatment of chronic hepatitis C in adult patients who are positive for serum HCV-RNA, including patients with compensated cirrhosis and/or who are co-infected with clinically stable HIV'. The preferred treatment regimen is in combination with ribavirin, but monotherapy is indicated in cases of intolerance or contraindication to ribavirin. Patients may not have been previously treated or their condition may have not responded to previous treatment with interferon alfa (pegylated or non-pegylated) alone or in combination with ribavirin. The recommended dose is 180 micrograms once a week, administered subcutaneously, for 16, 24 or 48 weeks depending on HCV genotype, baseline viral load and response to treatment. The recommended duration of peginterferon alfa-2a monotherapy is 48 weeks.

When peginterferon alfa-2a is given in combination with ribavirin, people with HCV genotype 1 or 4 infections who have detectable HCV RNA at week 4 (that is, there is not a rapid virological response) should receive 48 weeks of treatment. People with genotype 2 or 3 infections and undetectable HCV RNA at week 4 (that is, a rapid virological response) should receive 24 weeks of treatment.

An extension to the licence for peginterferon alfa-2a now means that some people with hepatitis C are eligible for shortened courses of treatment. People with HCV genotype 1 and a low viral load (equal to or less than 800,000 IU/ml) at the start of treatment, a rapid virological response at week 4 and undetectable HCV RNA at week 24 may complete treatment at week 24 rather than receiving the standard 48 weeks of therapy. The licence extension also allows people with HCV genotype 2 or 3 who have a low viral load (equal to or less than 800,000 IU/ml), undetectable HCV RNA by week 4 (that is, a rapid virological response) and undetectable HCV RNA at week 16 to stop treatment at week 16 rather than receiving the standard 24 weeks of therapy. People with HCV genotype 4 may be treated in line with the regimen for people with genotype 1, but without requiring a low viral load. People with genotype 5 or 6 should be treated for 48 weeks. People co-infected with HIV should also be treated for 48 weeks, regardless of genotype.

Re-treatment with peginterferon alfa-2a plus ribavirin may be offered to people whose hepatitis C has not shown an adequate response to treatment (non-response) or has responded but subsequently relapsed. Re-treated people should receive 48 weeks of treatment unless HCV RNA is still detectable at week 12, in which case treatment should be stopped. People with HCV genotype 1 whose condition has not responded to prior treatment with peginterferon alfa and ribavirin combination therapy and who are considered for re-treatment should receive 72 weeks of combination therapy.

A weekly course of treatment with peginterferon alfa-2a (180 micrograms) costs £126.91 (excluding VAT; BNF edition 59). Costs may vary in different settings because of negotiated procurement discounts.

Peginterferon alfa-2b (ViraferonPeg, Schering-Plough) has a UK marketing authorisation for 'the treatment of adult patients with chronic hepatitis C who are positive for HCV-RNA, including patients with compensated cirrhosis and/or co-infected with clinically stable HIV'. The preferred treatment regimen is in combination with ribavirin, but monotherapy with peginterferon alfa-2b is indicated in cases of intolerance or contraindication to ribavirin. Patients may not have been treated previously or their condition may have not responded to previous treatment with interferon alpha (pegylated or non-pegylated) in combination with ribavirin or interferon alfa monotherapy.

The recommended dose of peginterferon alfa-2b is 1.5 micrograms/kg body weight once a week, administered subcutaneously, for 24 or 48 weeks depending on HCV genotype, viral load at the start of treatment and response to treatment. People with HCV genotype 1 who have undetectable HCV RNA at week 12 (that is, who have an early virological response) should receive 48 weeks of treatment with peginterferon alfa-2b. People with a genotype 1 infection without an early virological response are considered unlikely to have a sustained virological response, and consideration should be given to withdrawing treatment. People with HCV genotype 4 should be treated with the same regimen as for genotype 1 infections. People with HCV genotype 2 or 3 infections should be treated for 24 weeks. People co-infected with HIV should be treated for 48 weeks regardless of HCV genotype.

Following a licence extension for peginterferon alfa-2b, some people with hepatitis C are eligible for shortened courses of treatment. People with HCV genotype 1 and a low viral load (below 600,000 IU/ml) at the onset of treatment and who have undetectable HCV RNA at both week 4 and week 24 of treatment can stop treatment at 24 weeks. The marketing authorisation notes that a shortened course of 24 weeks of treatment may be associated with a higher risk of relapse than if treatment is given for 48 weeks. The marketing authorisation does not permit shorter treatment durations for people with HCV genotype 2 or 3 infections.

Re-treatment with peginterferon alfa-2b in combination with ribavirin is recommended in the marketing authorisation for people whose hepatitis C has not shown an adequate response to treatment (non-response) or has responded but subsequently relapsed. All people re-treated with peginterferon alfa-2b, irrespective of HCV genotype, who have undetectable serum HCV RNA at week 12 should receive 48 weeks of treatment. People re-treated with peginterferon alfa-2b in whom HCV RNA is still detectable at week 12 are unlikely to have a sustained virological response after 48 weeks of therapy.

A weekly course of peginterferon alfa-2b (average of 120 micrograms) costs £162.60 (excluding VAT; BNF 59). Costs may vary in different settings because of negotiated procurement discounts.

Two forms of ribavirin (Copegus, Roche Products; Rebetol, Schering-Plough) are currently available. Each product is indicated for the treatment of chronic hepatitis C and must be used only as part of a combination regimen with peginterferon alfa or interferon alfa. Ribavirin monotherapy must not be used. Each product is licensed for use only in combination with the interferon products made by the same manufacturer. The recommended doses of ribavirin range from 800 to 1,400 milligrams, depending on body weight. The dose of Copegus also varies according to HCV genotype: 800 milligrams per day for genotype 2 or 3 infections and 1,000 or 1,200 milligrams per day for genotype 1, 4, 5 or 6 infections (1,000 milligrams for body weights below 75 kg and 1,200 milligrams for body weights of 75 kg or more). Both forms of ribavirin are taken orally each day in 2 divided doses.

The weekly cost of Copegus is £111 for HCV genotype 1 infections (based on 1,200 milligrams per day for an average body weight of 79 kg) and £74 for HCV genotype 2 or 3 infections (based on 800 milligrams per day). The weekly cost of Rebetol is £68, based on 1,000 milligrams per day for an average body weight of 79 kg. Costs exclude VAT and are from BNF 59. Costs may vary in different settings because of negotiated procurement discounts.

The cost of treatment with peginterferon alfa-2a plus ribavirin (Copegus) is estimated to be £3,215 for 16 weeks or £4,824 for 24 weeks of therapy (for people with genotypes 2 or 3), or £11,425 for 48 weeks of therapy (for people with genotypes 1 or 4). For people treated with peginterferon alfa-2b plus ribavirin (Rebetol), the cost is £5,540 for 24 weeks or £11,081 for 48 weeks of therapy (for people with genotype 1). Acquisition costs are from BNF 59. Costs may vary in different settings because of negotiated procurement discounts.

The most common adverse effects associated with peginterferon-based anti-viral treatments include influenza-like symptoms such as headache, fatigue and fever, as well as insomnia, anorexia, dermatological symptoms, nausea, vomiting and depression. The adverse effects of anti-viral treatment for HCV, notably depression, may be more pronounced in people co-infected with HIV. For full details of adverse effects and contraindications, see the summaries of product characteristics.