Expert Analysis /Impact of Higher-Dose Ribavirin on SVR

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Expert Analysis /Impact of Higher-Dose Ribavirin on SVR

Impact of Higher-Dose Ribavirin on SVR

Tram T. Tran, MD:Regarding approved therapies for hepatitis C, several reports have indicated that higher SVR rates are achieved with the use of higher doses of ribavirin[32,33] and 2 studies presented at the 2009 AASLD meeting addressed this question.

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kThe randomized phase IV PARADIGM trial compared the safety and efficacy of standard-dose ribavirin (800 mg/day) with high-dose ribavirin (1000-1200 mg/day), each in combination with peginterferon alfa-2a for the treatment of patients (N = 410) coinfected with genotype 1 HCV and HIV (Capsule Summary 34] Patients coinfected with HCV/HIV have been reported to achieve lower rates of SVR with combination peginterferon/ribavirin therapy relative to HCV-monoinfected patients.[32,35]The overall SVR rate for patients receiving standard ribavirin dosing (n = 135) was 19% vs 22% for those receiving the higher ribavirin dose (n = 275). Therefore, in this HCV/HIV-coinfected patient population, SVR rates were equivalent with both ribavirin

doses (odds ratio: 1.15; P = .6119). There was a 12% discontinuation rate in both treatment arms for safety reasons, and the overall proportion of patients who withdrew from the study prematurely was 59% with standard-dose ribavirin and 57% with high-dose ribavirin. Approximately 25% to 26% of patients withdrew for insufficient treatment response. It is interesting that the discontinuation rates were so high in this coinfected population. That might be an area of opportunity for improvement; however, ribavirin dose did not impact response rates or discontinuation rates./

Expert Analysis

/ R. , MD:The PROGRESS study conducted by Reddy and colleagues[36] was another analysis of high-dose ribavirin. This study was following up on a smaller, randomized phase II trial that compared standard doses of peginterferon alfa-2a and ribavirin with higher doses of either or both agents in a difficult-to-treat population of patients monoinfected with genotype 1 HCV who had high baseline HCV RNA (> 800,000 IU/mL) and weighed > 85 kg.[37] The data from the original study suggested that the combination of higher-dose peginterferon and higher-dose ribavirin was associated with improved response rates. Based on these findings, the PROGRESS study assessed both higher induction doses of peginterferon alfa-2a (360 μg/week for initial 12 weeks) and higher ribavirin dosing (1200 mg/day vs 1400-1600 mg/day) in 1175 genotype 1

HCV–infected patients with baseline HCV RNA ≥ 400,000 IU/mL and body weight ≥ 85 kg. The data showed that there was no benefit to higher-dose peginterferon alfa-2a, higher-dose ribavirin, or the combination of higher doses of both agents.

kTherefore, the overall conclusion from both the PARADIGM and PROGRESS trials is that the concept of induction dosing with peginterferon and/or higher-dose ribavirin does not appear to be efficacious.

http://Hepatitis Cnewdrugs.blogspot.com/2010/06/expert-analysis-impact-of-higher-dose.html