Randomized comparison of 12 or 24 weeks of peginterferon α-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection

Abstract

Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator-initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short-term therapy. Three hundred eighty-two genotype 2/3-infected patients [intention-to-treat (ITT) population] at 31 centers in Denmark, Finland, Norway, and Sweden were randomized to 12 or 24 weeks of peginterferon ␣-2a (180 g/week) plus ribavirin (800 mg/day). Twelve weeks of therapy was inferior to 24 weeks in the ITT population (sustained viral response [SVR] rates: 59% versus 78%, P < 0.0001) and in the subgroups of patients infected with genotype 2 (56% versus 82%, P ‫؍‬ 0.006) or 3 (58% versus 78%, P ‫؍‬ 0.0015). These differences were observed regardless of the fibrosis stage. Age and HCV-RNA levels on days 7 and 29 were independent predictors of SVR. Short-term treatment was useful in patients < 40 years old, especially if HCV-RNA was undetectable on day 29, and also in patients > 40 years old, provided that HCV-RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29. If neither of these two criteria were met for patients > 40 years old, 24 weeks of therapy was superior (P < 0.0001). Conclusion: Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus.

Optimal Duration of Pegylated Interferon Plus Ribavirin Therapy for Chronic Hepatitis C Genotype 3 Patients who do not Achieve Rapid Virological Response

“…20 With a standard 24 week course of therapy, SVR rate of 80-91% has been reported in RVR achievers whereas RVR non-achievers have 36-62% SVR rate. [8][9][10][11][12]20 Similar results were noted in the present study where the SVR rates with standard 24 week therapy in RVR achievers and RVR non-achievers were 91.5% and 52.3% respectively. These data emphasize the need for extended therapy in CHC G3 patients who do not achieve RVR.…”

“…7 However, in their study, analysis was done based on early virological response (EVR) and SVR, as the concept of rapid virological response (RVR) had not evolved by that time. After the concept of RVR evolved, it was noted that G-3 patients who do not achieve RVR have significantly lower (36-62%) SVR rates with the standard 24 week PEG-RBV therapy, [8][9][10][11][12] suggesting that extension of therapy is required in this subgroup of patients. However, the appropriate duration and the benefit of extended response guided PEG-RBV therapy for genotype 3 patients who do not achieve RVR has not been addressed adequately in literature.…”

Variants of the inosine triphosphate pyrophosphatase gene and relapse risk following treatment for HCV genotype 2/3

“…3,4 Because the RVR was reported as the most important predictor of SVR in HCV G2-infected patients, even when interleukin-28B variants were taken into consideration, 5,6 and ITPA variants were reported not to increase SVR in G2/3-infected patients with higher dose of RBV, 7 it is interesting to know whether the RVR is associated with ITPA variations and SVR in the present study of the NORDynamIC trial. 4 Particularly, because RVR is currently the most important factor for individualized therapy for G2/3-infected patients, the effect of the ITPA variants on determining the duration of Peg-IFN/RBV therapy for patients with or without RVR deserves to be explored.…”

Treatment of hepatitis C virus infection: Updated Swedish Consensus recommendations

“…HCV RNA below 1000 IU/ml at d 7 prior to the second peg-IFN dose, treatment duration may be shortened to 12Á16 weeks, provided that dose reductions can be avoided [28,29]. Patients with detectable HCV RNA at week 4, but undetectable at week 12 (cEVR), have a lower SVR rate when treated for 24 weeks than those who have achieved negative HCV RNA already at week 4.…”