HCV Consults: Volume 1, Number 1

Paradigm Shift in HCV Treatment

Issue: January 2015

Physicians seldom experience a paradigm shift as great as that transpiring in HCV therapy. With the approval last fall of 2 new direct-acting antiviral agents (DAAs) — simeprevir, a protease inhibitor, and sofosbuvir, a nucleotide analogue polymerase inhibitor — the protease inhibitors approved to great acclaim less than 3 years ago, telaprevir and boceprevir, have essentially ceased being prescribed in the United States. Indeed, their use is expressly discouraged for any clinical indication by the new American Association for the Study of Liver Diseases/Infectious Diseases Society of America recommendations (www.hcvguidelines.org).

For patients with HCV genotype 2 (G2) and G3, we have the first approved oral, inter-feron-free regimen of sofosbuvir and ribavirin. Although eradication of HCV G3 proved more challenging than expected from phase 2 data, extension of therapy to 24 weeks resulted in markedly increased rates of sustained virologic response (SVR), compared with shorter regimens in all populations except HCV G3 treatment-experienced cirrhotic patients. The higher relapse rates after 12 weeks of treatment in HCV G3, despite similarly rapid rates of on-treatment viral suppression, may be related to whatever factors promote the viral steatosis associated with HCV G3 on liver biopsy. The adverse impact of cirrhosis in treatment-experienced HCV G3 patients on this regimen is reminiscent of the impact of cirrhosis on response to interferon-based regimens.

HCV G1 infection is more complicated. The newly approved regimens, in which peginterferon and ribavirin are combined with simeprevir or sofosbuvir, represent improvements over boceprevir and telaprevir with regard to tolerability, convenience, duration of therapy and efficacy. If a combination of either DAA with peginterferon and ribavirin were the only new development in the next several years, these regimens would each be hailed as a new plateau in HCV therapy. However, this “new plateau” will likely also be the “last gasp” for interferon-based therapy. Recent phase 3 data on all-oral regimens applied to a broad HCV G1-infected population highlight extremely high SVR rates, excellent safety profiles, and very low rates of virologic failure. FDA approval is expected later this year, putting an end to the era of interferon and the question about whether to treat now or wait.

Clinicians have noticed that, for the first time, DAAs of different classes are actually available, although not approved for use together. Based on excellent results of the phase 2 COSMOS trial, the off-label oral combination of simeprevir and sofosbuvir, with or without ribavirin, has been recommended by the AASLD/IDSA for interferon-ineligible, treatment-naïve patients with HCV G1, and for treatment-experienced patients regardless of interferon eligibility. Discussions with patients should acknowledge the off-label nature of the combination, address the status of the patient’s liver disease, review the data available thus far and note the timelines toward anticipated approval of regimens that have already completed phase 3 trials.

This CME publication brings together experts in hepatology and gastroenterology to explore these new therapies for HCV in greater detail and discuss management of various genotypes, providing health care practitioners with vital information about utilizing new DAAs in their clinical practice.

Learning Objectives:

Upon completion of this activity, participants should be able to:

Apply evidence-based medicine and clinical data to determine when and how to initiate HCV treatment in order to individualize care and improve patient health and outcomes.
Evaluate multiple types of HCV patients for characteristics which impact treatment selection, duration of therapy, and address cost considerations and potential barriers to cure.
Implement new regimens for HCV by evaluating evidence-based clinical data on the safety and efficacy of new HCV treatment regimens to assist in clinical decision-making.

Click here to see the Education Lab Activity.

Overview

Author(s)/Faculty: Ira M. Jacobson, MD; Paul Martin, MD; Jordan J. Feld, MD, MPH; Camilla S. Graham, MD, MPH; Joseph K. Lim, MD; Mary Olson, DNP, ANP
Type: Monograph
Articles/Items: 9
Release Date: 4/1/2014
Expiration Date: 4/1/2015
Credit Type: CME
Number of Credits: 1.5
Cost: Free
Provider: Vindico

CME Information

Sponsorship Statement: This continuing medical education activity is sponsored by Vindico.
Support Statement: This activity is supported by educational grants from AbbVie and Genentech.
Target Audience: The intended audience for this activity is gastroenterologists, hepatologists, infectious disease specialists, nurse practitioners, physician assistants and other health care professionals involved in the treatment of patients with Hepatitis C virus (HCV).