Pegylated-interferon plus ribavirin therapy in the treatment of CHC: individualization of treatment duration according to on-treatment virologic response

Abstract

Background:

Standard treatment of chronic hepatitis C (CHC) is peginterferon alfa (PEG-IFN alfa) plus ribavirin (RBV) for 48 weeks in patients infected with genotype 1, and 24 weeks for those infected with genotype 2 or 3. However, recent studies have shown that on-treatment markers of virologic response can be used to tailor treatment duration according to each patient’s response to therapy.

Aim:

To discuss the rationale for assessing on-treatment markers of virologic response to PEG-IFN alfa plus RBV.

Methods:

A literature search was conducted using MEDLINE and conference proceedings for clinical studies of reduced and extended treatment durations in the treatment of CHC.

Findings:

Patients infected with genotype 1 and low baseline viral load who have undetectable HCV RNA by week 4 can be effectively treated for 24 weeks without any decline in efficacy. Extended treatment duration of 72 weeks has been studied in various selected patient groups with genotype 1 infection who are slow to respond to treatment; however, data are conflicting regarding the patient subgroup that may benefit most from this strategy. Finally, selected HCV genotype 2 or 3 patients with undetectable HCV RNA at week 4 and other favorable prognostic features may be effectively managed with shorter (12 to 16 weeks) treatment duration. Further work is required to determine how the findings of this review relate to patients who do not fit with the enrollment criteria of randomized clinical trials or who require dose adjustment based on adverse tolerability. Care should also be exercised when comparing data between studies because of differences in design and patient populations.

Conclusion:

Evaluation of on-treatment markers of virologic response has revolutionized the treatment of CHC: implementation of these assessments in clinical practice is strongly supported by data from recent clinical studies, even in advance of formal recognition in treatment guidelines.

Key words::

• Chronic disease
• Hepatitis C
• Peginterferon
• Ribavirin
• Therapeutics

Transparency

Declaration of funding

Funding for the literature search, data collection and editorial assistance for this manuscript was provided by Schering Corp., now Merck & Co., Inc., Whitehouse Station, NJ, USA.

Declaration of financial/other relationships

S.Z. has disclosed that he is a consultant to Schering-Plough, Roche, Debiopharm, Boehringer, Merck, GlaxoSmithKline, Gilead, Bristol-Myers Squibb, Intermune, Novartis, Human Genome Sciences and Pharmasset. F.P. has disclosed that he is a consultant to Schering-Plough, Roche, Gilead, Bristol-Myers Squibb, Vertex, Wyeth, Pharmasset, Abbott, Valeant, Intermune, Idenix, Novartis, Human Genome Sciences, GlaxoSmithKline and Intarcia. S.Z. has disclosed that he is on the speakers bureau of Schering-Plough, Roche, Gilead, Bristol-Myers Squibb and Novartis. F.P. has disclosed that he is on the speakers bureau of Gilead, Novartis, Roche and Schering-Plough.

Some peer reviewers receive honoraria from CMRO for their review work. Peer reviewer 1 has disclosed that he/she has received research grants from Genzyme, Genentech and Alexion. He/she also has served as a consultant to Novartis. Peer reviewer 2 has disclosed no relevant financial relationships.

Acknowledgments

The authors thank Tim Ibbotson, PhD, Maribeth Bogush, PhD, and Claudette Knight, PharmD, for their literature search, data collection, and formatting assistance, which was funded by Schering-Plough Corporation, now Merck & Co.