Longer Interferon Treatment Raises Hepatitis C Cure Rate

Meta-analysis finds that extending pegylated interferon plus ribavirin to 72 weeks may improve sustained response rates for late-responder genotype 1 hepatitis C patients.

Current standard-of-care treatment for chronic hepatitis C virus (HCV) infection consists of pegylated interferon (Pegasys or PegIntron) plus ribavirin for either 24 weeks (for people with HCV genotypes 2 or 3) or 48 weeks (for hard-to-treat genotypes 1 or 4).

New direct-acting antiviral agents will usher in a new paradigm in hepatitis C treatment. The first 2 drugs out of the pipeline -- boceprevir and telaprevir -- were recommended for FDA approval in late April. While these agents will likely eventually be used in all-oral regimens, initially they will be combined with pegylated interferon/ribavirin.

Interferon-based therapy can be difficult to tolerate, however, with side effects including depression, flu-like symptoms, and anemia. Researchers have therefore explored response-guided therapy, using HCV viral load reduction at 4 or 12 weeks to predict whether an individual could achieve a cure with shorter therapy or, alternatively, is unlikely to achieve sustained response at all, so should avoid further futile therapy. Prolonged therapy for hard-to-treat or slow-responding patients has not been so well studied.

As described in the April 2011 Journal of Viral Hepatitis, M. Parikh from Baylor College of Medicine and colleagues performed a systematic review and meta-analysis of 5 studies, comparing outcomes with 48 weeks vs 72 weeks of interferon-based therapy for treatment-naive genotype 1 chronic hepatitis C patients with late virological response, defined as failure to achieve a significant reduction in HCV viral load by week 12 of treatment.

Results

• End-of-treatment response rates were statistically similar with extended 72-week and standard 48-week treatment, at 48% vs 56%, respectively (pooled odds ratio [OR] 0.85).
• However, sustained virological response (SVR) rates after completion of therapy were higher with 72 weeks compared with 48 weeks of treatment, at 32% vs 25%, respectively (pooled OR 1.67).
• The improvement in sustained response was attributable to a lower post-treatment relapse rate with extended duration therapy (35% vs 55%, respectively; OR 0.39).

"Extending the treatment duration from 48 to 72 weeks in genotype 1 infected patients with late virological response improves SVR," the study authors concluded. "Thus, therapy extension in genotype 1 late viral responders may be a consideration to improve treatment response."

However, they added, the proportion of patients with late virological response who might benefit from 72-week therapy "appears to be small."

This proportion will likely become even smaller with the advent of the direct-acting agents, which have been shown to shorten the required duration of therapy for many patients and to reduce the likelihood of relapse.

Investigator affiliations: Department of Internal Medicine, Baylor College of Medicine, Houston, TX; Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX; Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX.

5/10/11

Reference
M Parikh, A Singh, and G Sood. Extended treatment duration for treatment naive chronic hepatitis C genotype 1 late viral responders: a meta-analysis comparing 48 weeks vs 72 weeks of pegylated interferon and ribavirin. Journal of Viral Hepatitis 18(4):e99-103 (abstract). April 2011.