Peginterferon alfa-2b (PegIntron)

Purpose / DescriptionIn this multicenter study performed in the United States, investigators sought to evaluate the efficacy of peginterferon alfa-2b 1.5 mcg/kg weekly plus ribavirin starting at 1000 mg daily for 12 weeks followed by 800 mg daily among blacks compared with non-Hispanic whites. They reported significantly lower sustained virologic response (SVR) rates among blacks (19%) compared with whites (52%, p<0.001); this disparity in SVR rates was explained primarily by race, and not socioeconomic status or genotype. The types and frequency of adverse events were similar in the two groups. This study clearly showed that black patients wiht genotype 1 infection have a lower response to treatment with peginterferon plus ribavirin than non-Hispanic whites. 

Purpose / DescriptionThe IDEAL Study is one of the largest trials of both forms of peginterferon alfa, designed as a head-to-head comparison of the two forms of peginterferon alfa (2a versus 2b) and to also compare two doses of peginterferon alfa-2b. Treatment-naïve patients with genotype 1 infection were randomly assigned to one of three treatment arms: (1) standard-dose (1.5 mcg/kg) peginteferon alfa-2b plus ribavirin (800-1400 mg/day), (2) low-dose (1 mcg/kg) peginteferon alfa-2b plus ribavirin (800-1400 mg/day), and (3) standard-dose (180 mcg) peginteferon alfa-2a plus ribavirin (1000-1200 mg/day). Patients who had an early virologic response had markedly higher SVR rates than those who do not achieve an early virologic response. The rates of sustained virologic responses and the incidence of adverse effects did not differ substantially across these regimens.

Purpose / DescriptionThis randomized controlled trial is one of the largest to examine peginterferon alfa-2b; it compared two different doses of peginterferon alfa-2b plus ribavirin (1.5 mcg/kg per week plus 800 mg ribavirin versus 1.5 mcg/kg per week for 4 weeks followed by 0.5 mcg/kg per week of peginterferon alfa-2b plus weight-based ribavirin of 1000-1200 mg/day for 48 weeks). These arms were also compared with standard interferon-2b with ribavirin among 1,530 patients with previously untreated chronic hepatitis C (HCV). The sustained virologic response rate was highest among the patients in the higher 1.5 mcg/kg dosing of peginterferon alfa-2b (54%) compared with lower-dose peginterferon alfa-2b (47%, p=0.01) or standard interferon (47%, p=0.01). Most of the benefit in this regimen was observed in those with genotype 1 HCV infection.

Purpose / DescriptionThis study is one of the first to examine the efficacy of a response-guided approach to treatment duration, comparing a standard 24-week duration of pegIFN-2b at a dose of 1 mcg/kg weekly plus weight-based ribavirin 1000-1200 mg daily with a “variable-duration” arm that treated at the same doses but allowed patients who achieved HCV viral suppression at week 4 to stop therapy after 12 weeks in treatment-naïve patients with genotype 2 and 3 HCV infection; those patients who failed to suppress completed 24 weeks of therapy. This variable-duration approach appeared to be as effective as the standard duration, achieving sustained virologic response in 77% patients compared to 76% in the standard-duration arm, with lower rates of adverse events and treatment withdrawal.

Purpose / DescriptionThis phase 4 study was a single-arm, open-label trial that assessed the safety and efficacy of 24 weeks of peginterferon alfa-2b 1.5 mcg/kg once weekly plus weight-based ribavirin 800-1400 mg/day in treatment-naïve patients with genotype 2 or 3 HCV infection. A sustained virologic response (SVR) was achieved in 93% of genotype 2 and 79% of genotype 3 patients with this regimen, comparable to the historical SVR rate of 84% with 48 weeks of therapy among genotype 2 and 3 patients. A lower pre-treatment HCV viral level, treatment duration of at least 16 weeks and minimal or no steatosis (less than 5%) were all independent predictors of SVR. Adverse events that required dose reduction or treatment interruption occurred in 18% patients.

Purpose / DescriptionThis open-label trial randomized 412 HIV-HCV coinfected patients to either 48 weeks of peginterferon alfa-2b plus 800 mg ribavirin daily versus 48 weeks of standard interferon alfa-2b plus 800 mg RBV. The pegIFN-2b group had a higher rate of sustained virologic response compared with the control arm (27% versus 20%, p=0.047) with most of the benefit seen in patients with genotype 1 or 4. The absolute difference however was smaller than that noted in the peginterferon alfa-2a trials of coinfected patients. Tolerability of these regimens were comparable however the pegIFN-2b arm experienced more dose reductions due to clinical adverse events (16% versus 7%, p=0.004).

Purpose / DescriptionThis very large, prospective, open-label trial enrolled 5207 hepatitis C treatment-naive patients at 236 sites in the United States to examine the impact of weight-based or flat-dose ribavirin given with peginterferon alfa-2b. Patients in the study were randomized on a 1:1 basis to receive peginterferon alfa-2b plus flat-dose ribavirin or peginterferon alfa-2b plus weight-based ribavirin. At the beginning of the trial, all patients were scheduled to recieve 48 weeks of therapy, but the protocol was amended so that patients with genotype 2 or 3 were randomized to receive either 24 or 48 weeks of therapy. Overall,  SVR24 rates were higher in patients who received weight based ribavirin compared with flat-dose ribavirin.  When analyzing for gentoype 1 patients, those who received weight based ribavirin compared with flat-dose ribavirin (34% versus 29%).  WIth genotype 2 and 3 patients, no significant differences were observed with weight-based versus flat-dose ribavirin and extending treatment to 48 weeks did not significantly improve SVR rates. This study demonstrated a benefit of using weight-based ribavirin in combination with peginterferon alfa-2b when treating patients with gentoype 1 HCV, but not with genotype 2 or 3.