Chronic hepatitis C (CHC)

Treatment-naïve adult patients

The recommended dose for peginterferon alpha-2a is 180 micrograms once weekly given in combination with oral ribavirin or as monotherapy.

The dose of ribavirin to be used in combination with peginterferon alpha-2a is given in Table 1.

The ribavirin dose should be administered with food.

Duration of treatment – dual therapy with peginterferon alpha-2a and ribavirin

The duration of combination therapy with ribavirin for CHC depends on viral genotype. Patients infected with HCV genotype 1 who have detectable HCV RNA at week 4 regardless of pre-treatment viral load should receive 48 weeks of therapy.

Treatment for 24 weeks may be considered in patients infected with:

• genotype 1 with low viral load (LVL) (≤800,000 IU/ml) at baseline or
• genotype 4

who become HCV RNA negative at week 4 and remain HCV RNA negative at week 24. However, an overall 24 weeks treatment duration may be associated with a higher risk of relapse than a 48 weeks treatment duration. In these patients, tolerability to combination therapy and additional prognostic factors such as degree of fibrosis should be taken into account when deciding on treatment duration. Shortening the treatment duration in patients with genotype 1 and high viral load (HVL) (>800, 000 IU/ml) at baseline who become HCV RNA negative at week 4 and remain HCV RNA negative at week 24 should be considered with even more caution since the limited data available suggest that this may significantly negatively impact the sustained virologic response.

Patients infected with HCV genotype 2 or 3 who have detectable HCV RNA at week 4, regardless of pre-treatment viral load should receive 24 weeks of therapy. Treatment for only 16 weeks may be considered in selected patients infected with genotype 2 or 3 with LVL (≤800,000 IU/ml) at baseline who become HCV negative by week 4 of treatment and remains HCV negative by week 16. Overall 16 weeks of treatment may be associated with a lower chance of response and is associated with a higher risk of relapse than a 24-week treatment duration. In these patients, tolerability to combination therapy and the presence of additional clinical or prognostic factors such as degree of fibrosis should be taken into account when considering deviations from standard 24 weeks treatment duration. Shortening the treatment duration in patients infected with genotype 2 or 3 with HVL (>800,000 IU/ml) at baseline who become HCV negative by week 4 should be considered with more caution as this may significantly negatively impact the sustained virological response (see Table 1).

Available data for patients infected with genotype 5 or 6 are limited; therefore combination treatment with 1,000/1,200 mg of ribavirin for 48 weeks is recommended.

Table 1. Dosing recommendations for combination therapy for adult patients with chronic hepatitis C:

* RVR = rapid viral response (HCV RNA undetectable) at week 4 and HCV RNA undetectable at week 24
** RVR = rapid viral response (HCV RNA negative) by week 4 LVL = ≤800,000 IU/ml; HVL = >800,000 IU/ml
^a It is presently not clear whether a higher dose of ribavirin (e.g.1000/1200 mg/day based on body weight) results in higher SVR rates than does the 800 mg/day, when treatment is shortened to 16 weeks.

The ultimate clinical impact of a shortened initial treatment of 16 weeks instead of 24 weeks is unknown, taking into account the need for re-treating non-responding and relapsing patients.

The recommended duration of peginterferon alpha-2a monotherapy is 48 weeks.

Treatment-experienced adult patients

The recommended dose of peginterferon alpha-2a in combination with ribavirin is 180 mcg once weekly by subcutaneous administration. For patients <75 kg and 75 kg, 1000 mg daily and 1200 mg daily of ribavirin, respectively, and regardless of genotype, should be administered. Patients who have detectable virus at week 12 should stop therapy. The recommended total duration of therapy is 48 weeks. If patients infected with virus genotype 1, not responding to prior treatment with peginterferon and ribavirin are considered for treatment, the recommended total duration of therapy is 72 weeks.

HIV-HCV co-infected adult patients

The recommended dosage for peginterferon alpha-2a, alone or in combination with ribavirin, is 180 micrograms once weekly subcutaneously for 48 weeks. For patients infected with HCV genotype 1 <75 kg and ≥75 kg, 1000 mg daily and 1200 mg daily of ribavirin, respectively, should be administered. Patients infected with HCV genotypes other than genotype 1 should receive 800 mg daily of ribavirin. A duration of therapy less than 48 weeks has not been adequately studied.

Predictability of response and non-response with peginterferon alpha-2a and ribavirin dual therapy – treatmentnaïve patients

Early virological response by week 12, defined as a 2 log viral load decrease or undetectable levels of HCV RNA has been shown to be predictive for sustained response (see Table 2).

Table 2. Predictive value of week 12 virological response at the recommended dosing regimen while on peginterferon alpha-2a combination therapy in adult patients with chronic hepatitis C:

The negative predictive value for sustained response in patients treated with peginterferon alpha-2a in monotherapy was 98%.

A similar negative predictive value has been observed in HIV-HCV co-infected patients treated with peginterferon alpha-2a monotherapy or in combination with ribavirin (100% (130/130) or 98% (83/85), respectively). Positive predictive values of 45% (50/110) and 70% (59/84) were observed for genotype 1 and genotype ⅔ HIV-HCV co-infected patients receiving combination therapy.

Predictability of response and non-response with peginterferon alpha-2a and ribavirin dual therapy – treatmentexperienced patients

In non-responder patients re-treated for 48 or 72 weeks, viral suppression at week 12 (undetectable HCV RNA defined as <50 IU/ml) has been shown to be predictive for sustained virological response. The probabilities of not achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was not achieved at week 12 were 96% (363 of 380) and 96% (324 of 339), respectively. The probabilities of achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was achieved at week 12 were 35% (20 of 57) and 57% (57 of 100), respectively.

Peginterferon alpha-2a is administered subcutaneously in the abdomen or thigh. Exposure to peginterferon alpha-2a was decreased in studies following administration of peginterferon alpha-2a in the arm.