Genotype 2 (G2) and 3 (G3) chronic hepatitis C virus (HCV) have high sustained virologic response (SVR) rates to peginterferon (PEG-IFN) alfa and ribavirin and require shorter duration of treatment. The optimal dosing of ribavirin and differences between SVR in G2 and G3 is not yet known.

The aim of the current study was to determine the predictors of response to PEG-IFN alfa-2b (PegIntron) plus ribavirin in patients with HCV G2 and G3.

WIN-R was a multicenter, randomized, open-label, investigator-initiated trial in 225 US sites between 12/00 and 6/05.  

In this trial, adult, treatment-naïve HCV patients with compensated liver disease were randomized to receive PEG-IFN alfa-2b 1.5 μg/kg/week plus FD ribavirin (800 mg/day) or WBD ribavirin (800 mg/day for weight <65 kg, 1,000 mg/day for 65–85 kg, 1,200 mg/day for >85–105 kg, 1,400 mg/day for >105–125 kg).

G2 and G3 patients were also randomized to receive 24 or 48 weeks of therapy. HCV RNA was assessed at weeks 0, 24, 48 and 72.

The primary endpoint was SVR (absence of detectable HCV RNA at week 72) in patients ≥65 kg.

Results

• 1829 G2/3 patients were enrolled and randomized to WBD (24 wks n=317, 48 wks n=602) or FD (24 wks n=322, 48 weeks n=588).
• SVR rates were similar in the WBD and FD groups (62 vs 60%, respectively) and were higher in the 24-week group (68 vs. 65%) than the 48 weeks (60 vs. 58%, respectively) due to a higher dropout rate after 24 weeks of therapy with missing data in that group (SVR not known, treated as NR).
• G2 had a higher SVR and lower relapse rate than G3 (72 vs. 63% with 24 weeks of WBD therapy and 5 vs. 10%, respectively).
• G3 patients had higher SVR with WBD (57 vs. 52% in 24 week group) but this difference was not statistically significantly.
• Relapse rates were highest in G3 high viral load patients treated for 24 weeks (16%).
• Multivariate analyses revealed G2, less advanced fibrosis, and 24 weeks of therapy as significant predictors of SVR. Safety and rates of drug discontinuation were similar between the groups.
  

Based on these findings the authors conclude, “Compared to Genotype 1 patients, WBD ribavirin and 48 weeks of therapy offers less advantage to FD in combination with PEG-IFN alfa-2b, in patients with HCV genotype 2 and 3.”

“Compared to G2 patients, SVR rates are lower and relapse rates are higher for G3 patients. G3 patients may benefit from higher ribavirin dosing.”

05/23-06

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