In patients with chronic hepatitis C, a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly.
The anti-hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon-␣2a (PEG IFN␣2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase II study in treatment-naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-␣2a 180 g/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 g/week PEG IFN-␣2a. In patients with genotypes 1 and 4, the 600-and 1,000-mg combination treatments induced a continuous decay in viral load that reached ؊4.61 ؎ 1.88 and ؊4.75 ؎ 2.19 log 10 IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by ؊5.91 ؎ 1.11 and ؊5.89 ؎ 0.43 log 10 IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN-␣2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day). Conclusion: These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-␣2a.
A multicenter, open-label, phase 3 study was conducted in 337 patients with chronic hepatitis C virus (HCV) infection who had either not responded to previous interferon therapy or had relapsed after discontinuation of therapy with either consensus interferon (9 g) or interferon ␣-2b (3 million U) three times a week for 24 weeks. Patients were randomized to receive a higher dose of consensus interferon (15 g) administered subcutaneously three times a week for 24 or 48 weeks and then were observed for an additional 24 weeks. Patients who had relapsed after prior interferon therapy were more likely to have a sustained alanine aminotransferase response and HCV RNA response (as measured by reverse transcriptionpolymerase chain reaction with a sensitivity of F100 copies/mL) than were patients who had not responded to prior interferon therapy. For relapsers, the sustained HCV RNA response rate was 58% (48 weeks) and 28% (24 weeks). The sustained alanine aminotransferase response for relapsers was 52% (48 weeks) and 39% (24 weeks). The sustained HCV RNA response rate among prior nonresponders was 13% (48 weeks) and 5% (24 weeks), and the sustained alanine aminotransferase response rate for nonresponders was 17% (48 weeks) and 12% (24 weeks). The administration of 15 g of consensus interferon was well tolerated and was not associated with an increase in the incidence of side effects. These data demonstrate that re-treatment with 15 g of consensus interferon is safe and effective therapy for patients with chronic hepatitis C who have either not responded to previous interferon therapy or relapsed after discontinuation of interferon therapy. (HEPA-TOLOGY 1998;27:1136-1143.)Hepatitis C virus (HCV) is the most common cause of non-A, non-B viral hepatitis in the world. 1,2 The disease is insidious, and the majority of patients do not develop jaundice at its onset. 3,4 HCV is a major public health concern because of its propensity to progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 5,6 The mechanism for viral persistence is unknown because HCV is an RNA virus that is not integrated into the host genome. 7 One potential explanation for the high rate of chronic infection is that HCV escapes immunologic surveillance because of its high spontaneous mutation rate, which has been estimated at 10 Ϫ2 mutations/nucleotide/year. 8 The current approved therapies for hepatitis C in the United States consist of the alpha interferons. 9,10 These are a family of cytokines with antiviral and immunomodulatory properties. 11,12 However, less than half of patients treated with alpha interferons do not respond to treatment, and of those who demonstrate a response, up to approximately two thirds will relapse within 6 months of discontinuing therapy. 13,14 Thus, the overall sustained alanine transaminase (ALT) response rate to alpha-interferon therapy is approximately 15% to 20%. 10 Consensus interferon (CIFN; Amgen Inc., Thousand Oaks, CA) is a genetically engineered molecule derived by assigning the most commonly observed ...
The benefit of extending treatment duration with peginterferon (PEG-IFN) and ribavirin (RBV) from 48 weeks to 72 weeks for patients with chronic hepatitis C genotype 1 infection has not been well established. In this prospective, international, open-label, randomized, multicenter study, 1,428 treatment-naïve patients from 133 centers were treated with PEG-IFN alfa-2b (1.5 lg/kg/week) plus RBV (800-1,400 mg/day). Patients with detectable hepatitis C virus (HCV) RNA and a !2-log 10 drop in HCV RNA levels at week 12 (slow responders) were randomized 1:1 to receive 48 weeks (n 5 86) or 72 weeks (n 5 73) of treatment. Sustained virologic response (SVR) rates were 43% in slow responders treated for 48 weeks and 48% in slow responders treated for 72 weeks (P 5 0.644). Relapse rates were similar in slow responders treated for 48 or 72 weeks (47% versus 33%, P 5 0.169). The safety profile was similar in both treatment arms; serious adverse events leading to discontinuation of treatment were observed in 3.5% of slow responders treated for 48 weeks and 8.2% of those treated for 72 weeks. Among slow responders with a <2-log drop in HCV RNA at week 8, SVR was 39% in the 72-week arm and 19% in the 48-week arm. Conclusion: These data suggest that 48 weeks of therapy with PEG-IFN alfa-2b plus RBV (800-1,400 mg/day) should remain a standard-of-care treatment for treatment-naïve G1 slow responders. (HEPATOLOGY 2010;52:1201-1207
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