A randomized trial of prolonged high dose of interferon plus ribavirin for hepatitis C patients nonresponders to interferon alone

Abstract

Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.

Pegylated Interferon and Ribavirin Failures: Is Retreatment an Option?

“…Patients retreated with a different form of IFN showed a higher response rate (13.0-18.6%) [5,6]. When IFN nonresponders were treated with a combination of IFN and RBV, the resulting SVR was 13-21% [4,7] (higher with a 48-week treatment and higher in patients who were non-type 1 genotypes). The SVR increased to 25-40% when PEG IFN and RBV were used [1,8].…”

A randomized trial of induction doses of interferon alone or in combination with ribavirin or ribavirin plus amantadine for treatment of nonresponder patients with chronic hepatitis C

“…The rate of discontinuation and the rate of dose reduction were comparable to those reported for either standard IFN plus ribavirin therapy in naïve patients 22,23 or high IFN doses plus ribavirin. 20 In summary, our study demonstrated that patients with chronic hepatitis C who were nonresponders to previous antiviral treatments may achieve a sustained virologic response rate of approximately 12% if retreated with IFNα induction treatment followed by daily dose administration. The addition of ribavirin or ribavirin plus amantadine did not result in an improvement in the sustained virologic response.…”

“…It has recently been shown that patients who were nonresponders to one or two courses of standard recombinant or lymphoblastoid IFNα may achieve a response rate ranging from 23% to 33% if retreated with 5 MU of IFNα plus ribavirin three times a week for 48 weeks with or without a short induction period. 20 Unfortunately, in this trial, there was not a group of patients treated with a reinforced regimen of IFNα alone.…”

Current Trends in Pharmacy Benefit Designs: A Threat to Disease Management in Chronic Complex Diseases

“…47 If treatment is initiated before significant fibrosis, or scarring, in the liver occurs, more than 50% of patients have an opportunity for a sustained remission or even eradication of the virus. 48,49 The use of interferon-based treatment regimens has been shown to reduce the risk of liver-related deaths. When quality of life is considered, a cost-effectiveness study suggested that the economic benefits of treating chronic HCV with pegylated interferon alfa-2a/2b and ribavirin are comparable to other widely accepted medical therapies.…”