Christopher I. Wright

Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection

BACKGROUND Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations. METHODS We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48. RESULTS Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001). CONCLUSIONS In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.).

Modeling, Clinical and Virology Data From Phase 2 and 3 Studies Support 12-Week Telaprevir Duration in Combination With 24- or 48-Week Peginterferon/Ribavirin

assess the association of HBsAg loss with different clinical phases of HBV and coinfection with HCV or HDV. Method: A total of 3335 patients (2064 male, 1271 female; mean age: 39.5±12.8), who have been HBsAg positive for at least 1 year and those who followed up for at least 6 months are included in the study. HbsAg loss rates in different clinical phases and coinfection with HBV or HDV were assesed. Differences were determined by log-rank test. Results: Among this cohort; 1160 (34.7%) were inactive carriers, 1675 (50.2%) were chronic hepatitis B, 298 (8.8%) were HBV cirrhosis, 77 (2.3%) were chronic HDV hepatitis, 43 (1.2%) were compensated HDV cirhosis, 44 (1.31%) were co-infected with hepatitis B and C. HBsAg loss rates among different groups were depicted in Figure 1. During a mean follow-up period of median 198 week (range: 24–1306 week), annual Hbs Ag loss rates were 1.88% in HBV and HCV co-infection, 1.64% in inactive carriers, 1.14% in HBV cirrhosis, 0.52% in chronic hepatitis B, 0.64% in HDV. No difference of HBsAg loss was observed between compensated and decompensated cirrhosis. None of HDV cirrhotics had seroclearance. 58.5% of HBV and HCV coinfected, 59% of HDV infected, 20% of chronic hepatitis B patients who had loss of HBsAg were treated with interferon or pegylated interferon. Conclusion: Although HDV infection supresses HBV replication, it does not increase the HBsAg loss rates. However, co-infection with HCV increases the seroclerance rates. HBsAg loss was markedly higher among inactive carriers comparing to chronic hepatitis.