In the Journals

Harvoni efficacy constant in HCV genotype 1 trials

Data from a clinical trial showed that Harvoni for 12 or 24 weeks with or without ribavirin was safe and effective in treatment-experienced patients with hepatitis genotype 1 with cirrhosis.

These results add to previous studies that confirmed the efficacy of Harvoni (LDV/SOF; ledipasvir/sofosbuvir, Gilead Sciences) in patients with HCV genotype 1, including teenage patients, elderly patients and those coinfected with HBV.

“In this multinational real-world study in patients undergoing antiviral therapy in the U.S., Canada, Germany and Israel, [per protocol] analysis reveals excellent rates of SVR12 with LDV/SOF in [genotype 1 treatment-experienced] cirrhotic patients, with or without [ribavirin], and regardless of 12 or 24-week treatment duration,” Joseph K. Lim, MD, from Yale University School of Medicine, and colleagues wrote.

The HCV-TARGET prospective study included 667 adult patients with HCV genotype 1, clinical evidence of cirrhosis and a history of treatment with interferon-based antiviral therapy. Most patients (n = 610) completed 12 or 24 weeks of LDV/SOF treatment with or without ribavirin and had available virologic outcomes.

A significant proportion of patients had a history of treatment with direct-acting antivirals (27%), hepatic decompensation (40%) or orthotopic liver transplantation (14%).

Overall, 579 of the 610 patients achieved sustained virologic response at 12 weeks (93.8%), including 98% of patients treated with LDV/SOF for 12 weeks, 94.1% of patients treated with LDV/SOF for 24 weeks, 97.1% of patients treated with LDV/SOF and ribavirin for 12 weeks, and 95% of patients treated with LDV/SOF and ribavirin for 24 weeks.

The researchers observed lower SVR rates among patients with hepatic decompensation compared with compensated cirrhosis (92.2% vs. 96.6%), a history of orthotopic liver transplantation (92.8% vs. 95.3%), albumin less than 3.5 g/dL (90.8% vs. 96.9%) and total bilirubin higher than 1.2 mg/dL (89.7% vs. 96.8%).

Multivariate analysis showed that compensated cirrhosis compared with decompensated cirrhosis (OR = 2.41; 95% CI, 1.16-5.02), albumin of 3.5 g/dL or higher (OR = 3.15; 9% CI, 1.46-6.8) and total bilirubin of 1.2 mg/dL or less (OR = 3.34; 95% CI, 1.59-7) correlated with a higher SVR rate.

Twenty-six of the 667 initially enrolled patients discontinued treatment early due to adverse events or death (n = 10), lack of efficacy (n = 2) or administrative reasons (n = 14).

Reasons for discontinuation due to adverse events, each reported in one patient, included: atrioventricular block, metastatic breast cancer, hepatocellular carcinoma, intraventricular hemorrhage, multi-organ failure, septic shock and subdural hematoma; and hemolytic anemia, gastrointestinal perforation and road traffic accident among those treated with ribavirin. – by Talitha Bennett

Disclosure: Lim reports he received grant funding from BMS, Conatus, Genfit, Gilead, Hologic and Intercept; and receive consultant fees from AbbVie, BMS and Gilead. Please see the full study for the other authors’ relevant financial disclosures.

Data from a clinical trial showed that Harvoni for 12 or 24 weeks with or without ribavirin was safe and effective in treatment-experienced patients with hepatitis genotype 1 with cirrhosis.

These results add to previous studies that confirmed the efficacy of Harvoni (LDV/SOF; ledipasvir/sofosbuvir, Gilead Sciences) in patients with HCV genotype 1, including teenage patients, elderly patients and those coinfected with HBV.

“In this multinational real-world study in patients undergoing antiviral therapy in the U.S., Canada, Germany and Israel, [per protocol] analysis reveals excellent rates of SVR12 with LDV/SOF in [genotype 1 treatment-experienced] cirrhotic patients, with or without [ribavirin], and regardless of 12 or 24-week treatment duration,” Joseph K. Lim, MD, from Yale University School of Medicine, and colleagues wrote.

The HCV-TARGET prospective study included 667 adult patients with HCV genotype 1, clinical evidence of cirrhosis and a history of treatment with interferon-based antiviral therapy. Most patients (n = 610) completed 12 or 24 weeks of LDV/SOF treatment with or without ribavirin and had available virologic outcomes.

A significant proportion of patients had a history of treatment with direct-acting antivirals (27%), hepatic decompensation (40%) or orthotopic liver transplantation (14%).

Overall, 579 of the 610 patients achieved sustained virologic response at 12 weeks (93.8%), including 98% of patients treated with LDV/SOF for 12 weeks, 94.1% of patients treated with LDV/SOF for 24 weeks, 97.1% of patients treated with LDV/SOF and ribavirin for 12 weeks, and 95% of patients treated with LDV/SOF and ribavirin for 24 weeks.

The researchers observed lower SVR rates among patients with hepatic decompensation compared with compensated cirrhosis (92.2% vs. 96.6%), a history of orthotopic liver transplantation (92.8% vs. 95.3%), albumin less than 3.5 g/dL (90.8% vs. 96.9%) and total bilirubin higher than 1.2 mg/dL (89.7% vs. 96.8%).

Multivariate analysis showed that compensated cirrhosis compared with decompensated cirrhosis (OR = 2.41; 95% CI, 1.16-5.02), albumin of 3.5 g/dL or higher (OR = 3.15; 9% CI, 1.46-6.8) and total bilirubin of 1.2 mg/dL or less (OR = 3.34; 95% CI, 1.59-7) correlated with a higher SVR rate.

Twenty-six of the 667 initially enrolled patients discontinued treatment early due to adverse events or death (n = 10), lack of efficacy (n = 2) or administrative reasons (n = 14).

Reasons for discontinuation due to adverse events, each reported in one patient, included: atrioventricular block, metastatic breast cancer, hepatocellular carcinoma, intraventricular hemorrhage, multi-organ failure, septic shock and subdural hematoma; and hemolytic anemia, gastrointestinal perforation and road traffic accident among those treated with ribavirin. – by Talitha Bennett

Disclosure: Lim reports he received grant funding from BMS, Conatus, Genfit, Gilead, Hologic and Intercept; and receive consultant fees from AbbVie, BMS and Gilead. Please see the full study for the other authors’ relevant financial disclosures.