• Liver Conditions
• Hepatology Clinical Trials Viral Infections

• Liver Conditions
• Hepatology Clinical Trials
• Hepatology
• Viral Infections

Treatment of cirrhotic, hepatitis C virus (HCV) genotype 1 (GT-1)-infected patients with a twice-daily oral regimen involving a single tablet of 3 direct-acting antiviral agents - the HCV NS3/4A serine protease inhibitor ABT-450 at 150 mg plus ritonavir 100 mg plus the NS5A inhibitor ombitasvir 25 mg - along with a tablet of dasabuvir 250 mg and a tablet of ribavirin yields high rates of sustained virologic response 12 weeks following conclusion of treatment (SVR12). The high SVR12 rates occur regardless of the baseline characteristics of the patients. The findings of the large, international, phase 3 TURQUOISE-II trial were presented by Michael Fried, MD, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. The findings of the TURQUOISE-II have been published [Poordad F et al. New Engl J Med. 2014].

Cirrhosis, high-level HCV viremia, and interleukin 28B (IL28B) non-CC genotype have been linked with lower SVR rates [Manns M et al. Lancet 2014]. These data, however, have come from small patient subsets, and information on SVR rates in difficult-to-treat populations, like null responders, is scant [Afdhal N et al. New Engl J Med. 2014]. TURQUOISE-II sought to evaluate the influence of baseline characteristics on treatment outcomes in HCV GT-1-infected patients with compensated cirrhosis. Patients (n = 380) were randomized to treatment with the direct-acting antiviral regimen of ABT-450 plus ritonavir plus ombitasvir along with dasabuvir, with the inclusion of 1000 or 1200 mg ribavirin according to body weight, for either 12 weeks (n = 208) or 24 weeks (n = 172). SVR 12 was assessed at week 24 and 36.

All included patients had received ≥ 1 dose of the drugs. Influential factors that were examined included viral factors (HCV RNA level, HCV subtype), host factors (age, sex, body mass index (BMI), IL28B genotype status, prior treatment, and histories of diabetes, depression/bipolar disorder, and intravenous drug use), and disease factors (serum albumin, platelet count, serum alpha-fetoprotein).

Baseline characteristics in the 12- and 24-week arms were comparable in terms of sex, ethnicity, mean age, mean BMI, IL28B non-CC genotype, treatment-naïve/ experienced proportions, platelet count, serum albumin, and Child-Pugh score. The overall SVR12 rates were high.

SVR12 was achieved in 91.6% (239/261) and 99.2% (118/119) of the genotype 1a and 1b patients, respectively. The rate was not significantly lower in the 12-week arm (91.8%; 191/208) compared with the 24-week arm (96.5%; 166/172). Consistently high viral response rates were evident at 12 and 24 weeks according to age (< 65 years and ≥ 65 years), sex (male and female), body mass index (< 30 kg/m² and ≥ 30 kg/m²), interleukin 28-B (IL28B) genotype, HCV subtype, baseline viral load (< 800 000 IU/ mL and ≥ 800 000 IU/mL), prior peglyated interferon and ribavirin treatment, alfa-fetoprotein (< 20 ng/mL and ≥ 20 ng/mL), and histories of diabetes, intravenous drug use, and depression/bipolar disorder.

SVR12 was not achieved in 23 patients (17 in the 12-week arm and 6 in the 24-week arm). Associated factors as determined in a logistic regression analysis were IL28B TT genotype (P = .021), prior null response (P = .038), and HCV genotype 1a (P = .046). Trends were evident for alfa-fetoprotein (P = .059) and treatment duration (P = .066). Overall, 2.1% of patients discontinued treatment because of adverse events.

The interferon-free regimen comprising the direct-acting antiviral regimen of ABT-450 plus ritonavir plus ombitasvir along with dasabuvir, plus ribavirin produced high SVR12 rates in a broad range of treatment-naïve and -experienced cirrhotic patients. Importantly, host, viral, and disease characteristics were not influential.

• © 2014 MD Conference Express®