Pegylated Interferon (PEG IFN) 2a and 2b for Chronic Hepatitis C
| PEG IFN-α2b | PEG IFN-α2a | |
|---|---|---|
| PEG size | 12 kD linear | 40 kD branched |
| Elimination half-life | 54 h | 65 h |
| Clearance | 725 mL/h | 60 mL/h |
| Dose | 1.5 µg/kg (weight-based) | 180 µg |
| Storage | Room temperature | Refrigerated |
Ribavirin dose Genotype 1 Genotype 2/3 |
800-1400 mga 800 mg |
1000-1200 mgb 800 mg |
Duration of therapy Genotype 1 Genotype 2/3 |
48 weeks 48 weeksc |
48 weeks 24 weeks |
Efficacy of combination therapyd Genotype 1 Genotype 2/3 | 54% 40-42% 82% | 56% 41-51% 76-78% |
aIn the registration trial for PEG IFN-α2b plus ribavirin, the optimal regimen was 1.5 µg of PEG IFN plus 800 mg of ribavirin; however, a post hoc analysis of this study suggested that higher ribavirin doses are better. In subsequent trials of PEG IFN-α2b with ribavirin in pts with genotype 1, the following daily ribavirin doses have been validated: 800 mg for pts weighing <65 kg, 1000 mg for pts weighing >65-85 kg, 1200 for pts weighing >85-105 kg, and 1400 mg for pts weighing >105 kg.
b1000 mg for pts weighing <75 kg; 1200 mg for pts weighing ≥75 kg.
cIn the registration trial for PEG IFN-α2b plus ribavirin, all pts were treated for 48 weeks; however, data from other trials of standard interferons and the other PEG IFN demonstrated that 24 weeks suffices for pts with genotypes 2 and 3. For pts with genotype 3 who have advanced fibrosis/cirrhosis and/or high-level HCV RNA, a full 48 weeks is preferable.
dAttempts to compare the two PEG IFN preparations based on the results of registration clinical trials are confounded by differences between trials of the two agents in methodologic details (different ribavirin doses, different methods for recording depression, and other side effects) and study-population composition (different proportion with bridging fibrosis/cirrhosis, proportion from the United States versus international, mean weight, proportion with genotype 1, and proportion with high-level HCV RNA). In the head-to-head comparison of the two PEG IFN preparations in the IDEAL trial reported in 2009, the two drugs were comparable in tolerability and efficacy. PEG IFN-α2b was administered at a weekly weight-based dose of 1.0 µg/kg or 1.5 µg/kg, and PEG IFN-α2a at a weekly fixed dose of 180 µg. For PEG IFN-α2b, daily ribavirin weight-based doses ranged between 800 and 1400 mg based on weight criteria (see footnote a, above), whereas for PEG IFN-α2a, daily ribavirin weight-based doses ranged between 1000 and 1200 mg (see footnote b, above). For the two PEG IFN-α2b study arms, ribavirin dose reductions for ribavirin-associated adverse effects were done in 200- to 400-mg decrements; for PEG IFN-α2a, the ribavirin dose was reduced to 600 mg for intolerability. Sustained virologic responses occurred in 38.0% of the low-dose PEG IFN-α2b group, 39.8% of the standard, full-dose PEG IFN-α2b group, and 40.9% of the PEG IFN-α2a group.
Abbreviations: HCV RNA, hepatitis C virus RNA; PEG, polyethylene glycol.