Prolonged Therapy with Pegylated Interferon/Ribavirin May Improve Odds of Sustained HCV Clearance

Recent studies have provided increasing evidence that among chronic hepatitis C patients treated with pegylated interferon plus ribavirin, rapid virological response (RVR) at week 4 is a good predictor of sustained virological response (SVR) 24 weeks after completion of therapy. Further, mathematic models suggest that in patients with genotype 1 HCV, the SVR rate directly correlates with the duration of treatment after HCV RNA becomes undetectable.

As reported at the 42nd Annual Meeting of the European Association for the Study of the Liver last month in Barcelona, Italian researchers conducted a study to evaluate SVR in relationship to RVR among 663 genotype 1 patients who received pegylated interferon plus ribavirin for either the standard 48-week course (n = 221) or individualized treatment durations of 24, 48, or 72 weeks (n = 442). In the individualized treatment group, those without RVR were treated for 48 or 72 weeks based on whether HCV RNA was undetectable at week 8 or week 12.

Results

• 236 patients (54%) in the individualized duration arm and 121 patients (55%) in the standard duration group had undetectable HCV RNA at week 8.
• At week 12, HCV RNA became undetectable for the first time in 50 patients in the individualized duration arm and 15 in the standard duration group.
• Proportions of non-responders at week 12 in the 2 arms were 155 (34%) and 85 (38%), respectively.
  Among patients who were HCV RNA negative at week 8, 111 of 318 (35%) in the individualized duration arm and 45 of 163 (28%) in the standard duration group achieved SVR (P = 0.12).
• When patients who became negative for the first time at week 12 were analyzed separately, the corresponding SVR rates were 32 of 50 (64%) and 5 of 15 (33%) (P = 0.07).
• In the latter subgroup, the only factor significantly associated with SVR was longer treatment duration (P = 0.0001; OR 1.68).
• Relapse rates did not differ significantly in the 2 treatment arms (5% vs 4%).
• Dropout rates were 15.3% in the individualized duration arm and 13.1% in the standard duration arm.

Conclusion

The investigators concluded that, “Results of this randomized controlled trial confirm that prolonging treatment [beyond] 48 weeks allows better SVR even in the subgroup of patients who clear HCV RNA at week 12 from the start of treatment.”

IRCCS Italy; Ospedale Canosa, Canosa, Italy; Ospedale Casarano, Canosa, Italy; Ospedale Venosa, Venosa, Italy; Universita di Palermo, Palermo, Italy; Policlinico Umberto i Dell’Universita, Rome, Italy; Hospital Sandro Pertini, Rome, Italy; Ospedali Riuniti Foggia, Foggia, Italy; Ospedale Brindisi, Brindisi, Italy.

05/11/07

Reference
A Mangia, N Minerva, D Bacca, and others. In pts who clear HCV RNA at week 12, SVR is higher after 72 than after 48 weeks tx: results of a randomized controlled trial (RCT). 42nd Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain. April 11-15, 2007.