ABT-450/r-Based Regimen for Genotype 1 HCV Infection: Is Ribavirin-Free as Effective?

Atif Zaman, MD, MPH

Overall, yes, although inclusion of ribavirin might be helpful in some patients with genotype 1a infection.

In recent phase III studies, the ABT-450/r-based regimen — a coformulated pill of ABT-450/r-ombitasvir (a ritonavir-boosted protease inhibitor plus an NS5A inhibitor; once daily) plus dasabuvir (a nonnucleoside polymerase inhibitor; 250 mg twice daily) and ribavirin (1000–1200 mg daily) — yielded response rates >95% in patients with hepatitis C virus (HCV) genotype 1 infection (NEJM JW Gastroenterol Apr 15 2014).

In two industry-funded, phase III trials, investigators assessed the efficacy of the ABT-450/r-based regimen with and without ribavirin. They randomized treatment-naive patients with genotype 1a HCV infection (419 patients) and genotype 1b HCV infection (305 patients) without cirrhosis to receive the regimen with ribavirin or placebo for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after therapy ended (SVR12). SVR12 rates were compared with historical controls: 80% for genotype 1b and 72% for genotype 1a. Assessment of the noninferiority of the ABT-450/r-based regimen without ribavirin (vs. with ribavirin) was based on a margin of 10.5 percentage points.

The overall SVR12 rates with and without ribavirin were 99.5% and 99.0%, respectively, in patients with genotype 1b HCV infection and 97.0% and 90.2% in patients with genotype 1a. The ribavirin-free regimen did not meet the criterion for noninferiority in either group. Although the regimen with ribavirin had a higher rate of adverse effects, including pruritus, nausea, insomnia, and anemia, the discontinuation rate was extremely low at 0.3%.

Citation(s):

Ferenci P et al. ABT-450/r–ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014 May 4; [e-pub ahead of print].