Peginterferon-α-2a (40kD) and Ribavirin in Patients with Chronic Hepatitis C
Background and aims: Addition of a 40kD polyethylene glycol moiety to interferon-α-2a [peginterferon-α-2a (40kD)] improves pharmacokinetic properties over those of standard interferon. We conducted a phase II study to assess the safety and initial efficacy of peginterferon-α-2a (40kD) plus ribavirin combination therapy in patients with chronic hepatitis C (CHC).
Methods: Twenty patients received open-label 180μg peginterferon-α-2a (40kD) subcutaneously once weekly and oral ribavirin 1000 or 1200mg daily for patients weighing <75 or ≥75kg, respectively, for a period of 24 weeks. Patients with hepatitis C virus (HCV) genotype 1 and a virological response at week 24 received study drugs for an additional 24 weeks.
Results: A sustained virological response, defined as undetectable HCV RNA 24 (i.e. <100 copies/ml) weeks after completing the therapy, was achieved in 50% of patients in an intent-to-treat analysis (6/16 genotype 1 and 4/4 genotype non-1). Adverse events were similar to those reported with unmodified interferon plus ribavirin combination therapy. Anaemia led to ribavirin dose reduction in five patients. Neutropenia led to dose reduction in three patients treated with peginterferon-α-2a (40kD).
Conclusions: The addition of ribavirin to a once-weekly peginterferon-α-2a (40kD) regimen should be investigated in larger clinical trials.
- 7.Xu Z-X, Hoffman J, Patel I, et al. Single-dose safety/tolerability and pharmacokinetic/pharmacodynamics (PK/PD) following administration of ascending subcutaneous doses of pegylated-interferon (PEG-IFN) and interferon α-2a (IFN α-2a) to healthy subjects [abstract]. Hepatology 1998; 28: 702CrossRefGoogle Scholar
- 8.Algranati NE, Sy S, Modi M. A branched methoxy 40 kDa polyethylene glycol (PEG) moiety optimizes the pharmacokinetics (PK) of peginterferon α-2a (PEG[40kDa] IFN αa-a) and may explain its enhanced efficacy in chronic hepatitis C (CHC) [abstract]. Hepatology 1999; 30: 190AGoogle Scholar
- 9.Pockros PJ, Heathcote EJ, Shiffman ML, et al. Efficacy of pegylated (40kDa) interferon alfa-2α (PEGASYS®) in randomized trials of patients with chronic hepatitis C, with and without cirrhosis: correlation of virological and histological responses with baseline liver histology and genotype [abstract]. Hepatology 2000; 32: 442ACrossRefGoogle Scholar
- 16.Rebetol [package insert]. Kenilworth (NJ): Schering-Plough; 1998Google Scholar
- 19.Fried MW, Shiffman ML, Reddy KR, et al. Pegylated (40 kDa) interferon alfa-2a (PEGASYS®) in combination with ribavirin: efficacy and safety results from a phase III, randomized, actively-controlled, multicenter study. Gastroenterology 2001; 1205 Suppl. 1: A55Google Scholar