Interferon Combo Regimen for HCV GT2,3?

Peginterferon Lambda-1a plus ribavirin (Lambda/RBV) may be a better treatment for chronic hepatitis C virus (HCV) genotype 2 or 3 infection than alfa-2a plus RBV (alfa/RBV) according to the results of a recent randomized controlled trial. The study, conducted by Graham Foster, PhD, of the Department of Hepatology at Queen Mary University of London, and colleagues, was published online in the journal SpringerPlus on August 19, 2016.

The authors compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection.

The primary outcome, sustained virologic response, was measured at week 12 (SVR12).

HCV genotype 2 or 3 infections, most common in South America, Asia (genotype 2), Europe, the United States, Australia, and southern Asia (genotype 3), were primarily treated with alfa/RBV. However, the researchers say, “Alfa/RBV therapy is subject to a number of limitations; among these are frequent, sometimes treatment-limiting adverse events (AEs) including hemolytic anemia and other cytopenias.”

Additionally, genotype 3 is associated with worse outcomes than genotype 2, and often has a lower sustained virologic response.

Although oral direct-acting antiviral (DAA) regimens are now becoming the more common treatment method, DAA options for genotypes 2 and 3 are limited, thus motivating researchers to seek alternatives.

The randomized, double-blind, multinational phase 3 study included 124 treatment centers from 18 countries.

There were 874 participants, and of those 353 were in the Lambda/RBV group; 349 in the Lambda/RBV + DCV group; and 172 in the alfa/RBV group.

“SVR12 was achieved by 83% in the Lambda/RBV + DCV group, 68% in the Lambda/RBV group, and 73% in the alfa/RBV group,” say the researchers, continuing, “In contrast, SVR12 for Lambda/RBV versus alfa/RBV did not meet prespecified non-inferiority criteria.”

SVR12 rates were better for the participants with genotype 2 HCV infections compared to those with genotype 3, with 90% of those with genotype 2 achieving SVR12, compared to 75% of those with genotype 3.

Although the researchers concluded that “12 weeks of treatment with Lambda/RBV and DCV gave a superior SVR12 rate compared with 24 weeks of alfa/RBV in the combined population of patients with genotype 2 or 3 infection,” they added that development was discontinued “due to the emergence of highly efficacious and well-tolerated all-oral DAA combination regimens.”