Positive and negative prediction of sustained virologic response at weeks 2 and 4 of treatment with albinterferon alfa-2b or peginterferon alfa-2a in treatment-naïve patients with genotype 1, chronic hepatitis C☆

Background/Aims

Albinterferon alfa-2b is a novel, long-acting, fusion polypeptide that is dosed q2wk or q4wk. The predictive value of early virologic response during albinterferon alfa-2b or peginterferon alfa-2a treatment was investigated in interferon-naïve patients with genotype 1, chronic hepatitis C.

Methods

Four hundred and fifty-eight patients were randomized to: albinterferon 900 or 1200μg q2wk, or 1200μg q4wk, or peginterferon 180μg qwk. HCV RNA was measured by real-time PCR. A linear exhaustive search algorithm was used to determine the best SVR prediction algorithm in the per-protocol population (n=368), with inclusion of key ITT analyses to assess impact.

Results

SVR rate: 54–67% (P=NS between arms). Rapid initial virologic response rate at week 2 (RIVR; viral decline >2log₁₀IU/mL) was 32–50% and gave rise to positive predictive value of 88–97% for SVR. No initial virologic response at week 4 (NIVR; viral decline <2log₁₀IU/mL; viral load >5.5log₁₀IU/mL) demonstrated a 100% negative predictive value for SVR. A sequential prediction algorithm based on viral kinetics at weeks 2 and 4 identified four prediction groups that reliably predicted SVR, positively or negatively, in 65–72% of patients.

Conclusions

Improved SVR prediction was obtained by integrating absolute levels and reduction of HCV RNA at treatment week 2 and 4. Patients with RIVR had a high likelihood of achieving SVR.

Abbreviations: HCV, hepatitis C virus, PEG-IFN, pegylated interferon, RBV, ribavirin, CHC, chronic hepatitis C, RIVR, rapid initial virologic response rate, SVR, sustained virologic response, NPV, negative predictive value, PPV, high positive predictive value, albIFN, albinterferon alfa-2b, VD, viral decline, VL, viral load

Keywords: albIFN, Albinterferon alfa-2b, CHC, Chronic hepatitis C, HCV, Hepatitis C virus, Peginterferon, Sustained virologic response, SVR