Peginterferon alfa-2a (Pegasys)

Purpose / DescriptionIn this phase 2 trial involving patients coinfected with HCV and HIV, investigators  randomized 133 subjects to receive a 48-week treatment course with either peginteferon alfa-2a plus ribavirin or standard interferon alfa-2a plus ribavirin. The ribavirin, was administered in both arms as a gradual dose escalation of 600 mg/day for 4 weeks, 800 mg/day for 4 weeks, and then 1000 mg/day thereafter. Among study participants, 86% were on antiretroviral therapy and 10% had cirrhosis. Treatment with peginteferon alfa-2a was associated with higher SVR rate than with standard interferon alfa-2a (27% versus 12%, p=0.03). Premature discontinuation occurred in 12% of patients in each arm. This study clearly established that peginteferon alfa-2a and ribavirin was superior to standard interferon alfa-2a and ribavirin in persons coinfected with HCV and HIV. 

Purpose / DescriptionThe phase 3, randomized, controlled APRICOT study is one of the sentinel trials of peginterferon alfa-2a in patients coinfected with HCV and HIV. Investigators randomized 868 HCV-HIV coinfected patients to one of three treatment arms, each 48 weeks in duration: (1) peginterferon alfa-2a plus ribavirin 800 mg/day, (2) peginterferon alfa-2a plus placebo, and (3) standard interferon alfa-2a plus ribavirin 800 mg/day. Among study participants, 84% were on antiretroviral therapy and 16% had cirrhosis. The combination of peginterferon alfa-2a and ribavirin generated significantly higher sustained virologic response rates compared with peginterferon alfa-2a monotherapy (40% versus 20%, p<0.001) and standard interferon alfa-2a plus ribavirin (40% versus 12%, p<0.001). The difference in SVR rates was most notable in patients with genotype 1 infection (29% versus 14% and 7% respectively, p<0.001). In addition, patients in the standard interferon arm had higher treatment discontinuation rates than patients in the peginterferon alfa-2a arms. This study clearly established that (1) peginteferon alfa-2a and ribavirin was superior to standard interferon alfa-2a and ribavirin in persons coinfected with HIV, and (2) the addition of ribavirin to peginterferon alfa-2a significantly improves SVR rates in persons coinfected with HIV. 

Purpose / DescriptionThis multicenter, phase 3, randomized, double-blind trial used a 2 x 2 factorial design to examine the efficacy of 24 versus 48 weeks of peginterferon alfa-2a plus ribavirin, as well as the difference between fixed low dose (800 mg/day) versus weight-based (1000 or 1200 mg/day) dosing of ribavirin in patients with chronic HCV infection. Investigators enrolled 1311 patients, among whom 740 had genotype 1 infection. In patients with genotype 1, significantly higher SVR24 rates were observed with weight-based ribavirin dosing (compared with fixed low dose ribavirin) and with 48 versus 24 weeks of therapy. Among patients with genotypes 2 or 3 infection, ribavirin dosing and duration of therapy did not significantly affect SVR rates. This study clearly demonstrated that treatment of genotype 1 HCV with peginterferon alfa-2a plus ribavirin generates significantly higher SVR24 rates when higher doses of ribavirin are used and patients receive a longer treatment duration.

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 examined the efficacy and safety of combination therapy with peginterferon alfa-2a plus ribavirin compared with peginterferon alfa-2a plus placebo (monotherapy) or standard interferon alfa-2a plus ribavirin. A total of 1,121  treatment-naïve patients with chronic hepatitis C were enrolled in the trial. Sustained virologic response (SVR) rate at 24 weeks post-treatment was greater among patients who received peginterferon alfa-2a  plus ribavirin than with either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy (56% versus 44% and 29% respectively, p<0.001). Independent predictors of SVR in this study included genotypes other than genotype 1, age less than 40 years, and body weight of 75 kg or less. The overall side effect profiles were similar between the three treatment arms. This study clearly established that (1) peginteferon alfa-2a and ribavirin was superior to standard interferon alfa-2a and ribavirin, and (2) the addition of ribavirin to peginterferon alfa-2a significantly improves SVR rates. 

Purpose / DescriptionIn this open label, phase 3 trial, investigators randomized 531 hepatitis C treatment-naïve patients with chronic hepatitis C to recieve a 48-week treatment course with peginterferon alfa-2a or standard interferon alfa-2a. Approximately 62% of the patients enrolled in the trial had genotype 1 HCV.  Compared with patients in the standard interferon alfa-2a arm, patients in the peginterferon alfa-2a arm had a higher end-of-treatment response (69% versus 28%, p=0.001) and higher sustained virologic response rates (39% versus 19%, p=0.001). The frequency and severity of adverse effects were similar between treatment groups, aside from a trend toward lower incidence of depression among patients who received peginterferon alfa-2a (16% versus 23% in the standard interferon arm). This trial clearly demonstrated the superiority of peginterferon alfa-2a over standard interferon alfa-2a.