Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

Abstract

, 15 and the North-C Group A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon ␣-2b (1.5 g/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n ‫؍‬ 148) or group B (n ‫؍‬ 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, ؊0.1 to ؉13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks. (HEPATOLOGY 2008;47:35-43.) A pproximately 55% of patients with chronic hepatitis C obtain a sustained virological response (SVR) after treatment with pegylated interferon alfa (PEG-IFN-␣) and ribavirin. 1,2 However, only a minority of those in need of therapy actually receive treatment, 3 primarily because of high medical costs and frequent and sometimes serious side effects. Thus, finding the appropriate treatment schedule for each chronic hepatitis C patient is important.Several factors have an impact on response to treatment, with hepatitis C virus (HCV) genotype being the single most important predictor of response. Those with genotype 1 infection have an SVR rate of 40% to 55%Abbreviations: ALT, alanine aminotransferase; APRI, aspartate aminotransferase-to-platelet ratio index; AST, aspartate aminotransferase; CI, confidence interval; HCV, hepatitis C virus; PEG-IFN-␣, pegylated interferon alfa; RVR, rapid virological response; SVR, sustained virological response. From the

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.…”

Practice guidelines for the treatment of hepatitis C: Recommendations from an AISF/SIMIT/SIMAST Expert Opinion Meeting

“…7. If no early virological response (a reduction of at least 2 log 10 in HCV-RNA in comparison with baseline) is achieved by week 12, HCV treatment should be discontinued as an SVR is unlikely (A-I) 8. Patients with genotypes 2 or 3, low viral loads (<400,000 U/mL) and mild fibrosis in whom HCV-RNA becomes undetectable in 4 weeks (a rapid virological response) may need only 24 weeks of therapy, but this can increase the relapse rate (A-III).…”

Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?

“…In a randomized study of 1311 CHC patients given only Peg-IFN + RBV, Hadziyannis et al [21] reported an SVR of approximately 80% in those infected with genotype 2 or 3 virus versus approximately 52% in those with genotype 1 virus. Several other studies [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] of CHC patients with genotype 2 or 3 virus, treated with either Peg-IFN or IFN, both administered with RBV, are summarized in Table 1 and show no better results with either IFN, when given in combination with RBV, for genotypes 2 and 3 viruses.…”