Hepatitis C Responds Better to Triple Antiviral Therapy

Larry Hand

November 26, 2012

Sustained virological response (SVR) rates for the most common chronic hepatitis C virus (HCV) infection may be "substantially higher" if newer triple-therapy regimens are administered compared with the standard dual-therapy approaches, according to a study published online November 26 in the Annals of Internal Medicine.

Roger Chou, MD, from the Oregon Health & Science University in Portland, and colleagues assessed 458 full-text studies identified through multiple databases and published between 1947 and 2012. The publications included randomized trials of antiviral treatments and cohort studies on clinical outcomes and SVR after antiviral treatment.

No study, however, assessed comparative clinical effectiveness of antiviral treatments because of the long time course for HCV complications to develop. The researchers instead used SVR rates as a surrogate endpoint because SVR after antiviral treatment "appears to be associated with improved clinical outcomes."

Dual therapy with pegylated interferon combined with ribavirin became the standard HCV treatment in the early 2000s, and the US Food and Drug Administration approved the antiviral agents boceprevir and telaprevir in 2011 for chronic HCV genotype 1; this genotype accounts for about 75% of HCV infection cases in the United States.

"Understanding the comparative effectiveness of antiviral regimens is critical for making informed treatment decisions for HCV infection," the researchers write. Their review focuses on comparative effectiveness for treatment-naive patients and on whether effectiveness varies according to clinical and demographic characteristics. They used "the absence of detectable HCV RNA in the serum six months after the end of a course of therapy" as their definition for SVR.

The researchers found that in 2 clinical trials (n = 1097 and 520) that evaluated the triple therapy of boceprevir, pegylated interferon alfa-2b, and ribavirin compared with dual therapy without boceprevir for HCV genotype 1, the triple therapy was associated with a greater likelihood for SVR than dual therapy alone (pooled relative risk [RR], 1.8 [95% confidence interval (CI), 1.6 - 2.1]; I 2, 0%; pooled absolute increase, 31 percentage points [95% CI, 23 - 39 percentage points]).

They also found that 3 trials (n = 189 - 250) concluded that a 24-week triple therapy regimen including telaprevir, pegylated interferon, and ribavirin was associated with a greater likelihood of SVR compared with a 48-week dual therapy without telaprevir (pooled RR, 1.5; 95% CI, 1.3 - 1.8; I 2, 0%).

The review includes many other findings. For example, in trials comparing dual therapy of ribavirin plus pegylated interferon alfa-2a (180 μg/kg/week) with alfa-2b (1.5 μg/kg/week), alfa-2b was associated with a lesser likelihood of SVR than alfa-2a (pooled RR, 0.87 [95% CI, 0.80 - 0.95]; I 2, 27%; pooled absolute difference, 8 percentage points [95% CI, 3 - 14 percentage points]).

"Across all antiviral regimens, absolute treatment response rates across regimens are lower in older patients, black patients, and patients with higher baseline viral load, genotype 1 infection, or more advanced fibrosis," the researchers write.

Limitations include that their analysis is based only on English-language articles and that pooled estimates based on a small number of trials should be interpreted cautiously.

The researchers conclude, "The relative ineffectiveness of dual therapy for genotype 1 infection has led to ongoing efforts to identify more effective treatments. Recent trials found triple therapy with boceprevir or telaprevir superior to dual therapy, with SVR rates approaching the 70–80 percent observed in trials of dual therapy for genotype 2 or 3 infection. This has important implications for treatment as well as for screening, since screening benefits depend in part on the effectiveness of available treatments."

This study was supported by the Agency for Healthcare Research and Quality. The authors have disclosed no relevant financial relationships.

Ann Intern Med. Published online November 26, 2012.