Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection

Abstract

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.)

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“…[173][174][175] Obesity does not have a similar negative impact on the response to newer protease-inhibitor based anti-viral regimens, [176][177][178][179][180] but the impact of insulin resistance and hepatic steatosis has not yet been investigated sufficiently. It is not known if the treatment of steatosis and steatohepatitis alters the natural history of other chronic liver diseases such as HCV and PBC.…”

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Cutaneous lesions from IFN-α-induced sarcoidosis: how do we reverse the effects?

“…However, a high index of suspicion is needed to establish an early diagnosis, and in the case of IFN-a, the use of a shorter duration of therapy and more effective combination regimens may eventually prevent or revert this clinical complication [19].…”