Peginterferon Alfa-2a/Ribavirin for 48 or 72 Weeks in Hepatitis C Genotypes 1 and 4 Patients With Slow Virologic Response

Background & Aims

This randomized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 μg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response (VR).

Methods

Patients with a rapid VR (RVR; undetectable hepatitis C virus [HCV]-RNA level (<50 IU/mL at week 4) were treated for 24 weeks, those with an early VR (EVR; no RVR but undetectable HCV-RNA level or ≥2-log₁₀ decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B; peginterferon alfa-2a was reduced to 135 μg/wk after week 48). Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24. The primary end point was relapse; sustained VR (SVR; undetectable HCV-RNA level after 24 weeks of follow-up evaluation) was a secondary end point.

Results

Of 551 genotype 1/4 patients starting treatment, 289 were randomized to group A (N = 139) or group B (N = 150). The relapse rate was 33.6% in group A (95% confidence interval [CI], 24.8%–43.4%) and 18.5% in group B (95% CI, 11.9%–27.6%; P = .0115 vs group A) and the SVR rate was 51.1% (95% CI, 42.5%–59.6%) and 58.6% (95% CI, 50.3%–66.6%; P > .1), respectively. The overall SVR rate was 50.4% (278 of 551; 95% CI, 46.2%–54.7%), including 115 of 150 patients with an RVR treated for 24 weeks and 4 of 78 patients without an EVR.

Conclusions

Extending therapy with peginterferon alfa-2a/ribavirin to 72 weeks decreases the probability of relapse in patients with an EVR. If they can be maintained on extended-duration therapy, SVR rates also may improve.

Abbreviations used in this paper: CI, confidence interval, EVR, early virologic response, PCR, polymerase chain reaction, RVR, rapid virologic response, SVR, sustained virologic response