Methods In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginter feron alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug. Results Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%). Conclusions Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, re gardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Phar maceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.)

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Telaprevir for retreatment of HCV infection.

Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide [1]. The long-term hepatic impact of HCV infection is highly variable, from minimal changes to chronic hepatitis, extensive fibrosis, and cirrhosis with or without hepatocellular carcinoma (HCC). The number of chronically infected persons worldwide may exceed 200 million, but most of them have no knowledge of their infection or of the ensuing hepatic condition. Clinical care for patients with HCV-related liver disease has advanced considerably during the last two decades, as a result of growing knowledge about the mechanisms of the disease, remarkable developments in diagnostic procedures, and advances in therapeutic and preventative approaches. Still, various aspects are not yet completely resolved. These EASL Clinical Practice Guidelines (CPGs) are intended to assist physicians and other healthcare providers, as well as patients and interested individuals, in the clinical decision-making process by describing optimal management of patients with acute and chronic HCV infections. These guidelines apply to therapies that are approved at the time of their publication. Several new therapeutic options have completed phase III development for patients infected with HCV genotype 1 and are currently awaiting licensing and approval in Europe and the United States. Therefore, the EASL CPGs on the management of HCV infection will be updated on a regular basis upon approval of additional novel therapies.

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EASL Clinical Practice Guidelines: Management of hepatitis C virus infection European Association for the Study of the Liver ⇑

Resistance to Direct Antiviral Agents in Patients With Hepatitis C Virus Infection

from less than 10% with the initial regimen of interferon monotherapy to more than 70% with current therapy. Moreover, many other drugs targeting viral or host factors are in development, and some will almost certainly be approved in the coming years. The questions of who should be treated and with what regimen will be increasingly complex to address and will require careful consideration. As therapy improves, systemwide identification and care of patients who need treatment will be the next challenge. Because most infected persons are unaware of their diagnosis, the Centers for Disease Control and Prevention recently recommended screening for HCV all persons born between 1945 and 1965. 2,3 It is anticipated that in the course of such a screening process, a large number of persons will be found to be infected with the virus; whether it will be possible to treat all these people is unclear. This article reviews the current therapy for HCV infection and the landscape of drug development.

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Current and future therapies for hepatitis C virus infection.

Antiviral strategies in hepatitis C virus infection.

https://www.gastrojournal.org/article/S0016-5085(10)01584-2/pdf

Telaprevir Is Effective Given Every 8 or 12 Hours With Ribavirin and Peginterferon Alfa-2a or -2b to Patients With Chronic Hepatitis C

Virological analysis of patients receiving Telaprevir administered Q8H or Q12H with Peginterferon-Alfa-2A or -Alfa-2B and Ribavirin in treatment-naive patients with Genotype I hepatitis C: study C208

Phase 2 study of Telaprevir administered Q8 or Q12H with Peginterferon-Alfa-2A or Alfa-2B and ribavirin in treatment-naive subjects with genotype 1 hepatitis C: week 4 interim results

https://www.journal-of-hepatology.eu/article/S0168-8278(10)60058-X/pdf

T2003 On-Treatment Response-Guided Therapy With Telaprevir Q8h or Q12h Combined With Peginterferon Alfa-2a or Peginterferon Alfa-2B and Ribavirin in Treatment-NaïVE Genotype 1 Hepatitis C (Study C208)

Koen De Backer

Papers

Telaprevir Is Effective Given Every 8 or 12 Hours With Ribavirin and Peginterferon Alfa-2a or -2b to Patients With Chronic Hepatitis C

Virological analysis of patients receiving Telaprevir administered Q8H or Q12H with Peginterferon-Alfa-2A or -Alfa-2B and Ribavirin in treatment-naive patients with Genotype I hepatitis C: study C208

Phase 2 study of Telaprevir administered Q8 or Q12H with Peginterferon-Alfa-2A or Alfa-2B and ribavirin in treatment-naive subjects with genotype 1 hepatitis C: week 4 interim results

T2003 On-Treatment Response-Guided Therapy With Telaprevir Q8h or Q12h Combined With Peginterferon Alfa-2a or Peginterferon Alfa-2B and Ribavirin in Treatment-NaïVE Genotype 1 Hepatitis C (Study C208)