Eight-week drug combo regimen maintains SVR in real-world setting

An eight-week regimen of ledipasvir and sofosbuvir can reduce costs without compromising outcomes for treatment-naïve patients infected with genotype 1 hepatitis C virus (HCV).

Based on the availability of highly effective direct-acting antiviral (DAA) agents, treatment of naïve genotype 1 HCV patients with these agents is now considered to be a cost-effective strategy. The fixed dose combination of ledipasvir and sofosbuvir is approved by the Food and Drug Administration (FDA) for the treatment of genotype 1 HCV infection in treatment-naïve patients with and without cirrhosis, based on two registration trials, ION-1 and ION-3.

The FDA included consideration of 8 weeks of ledipasvir/sofosbuvir in genotype 1 treatment-naïve patients without cirrhosis who have a pre-treatment viral load of <6 million IU/mL. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar sustained virologic response (SVR) for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks.

Now an observational, real-world cohort study confirms treatment success following 8 weeks of the ledipasvir/sofosbuvir combination for treatment-naïve genotype 1 HCV patients.

“Reducing the duration of treatment for these patients could result in significant cost savings and possibly allow more patients to receive much needed anti-viral therapy,” co-author Zobair Yousonni, MD, MPH, chairman of the department of medicine at Inova Fairfax Hospital in Annandale, Virginia, told Medical Economics.

The researchers published their results in September 2017 Alimentary Pharmacology & Therapeutics.

The study included a total of 826 patients who were treated for either 8 weeks (252 patients) or 12 weeks (574 patients) with ledipasvir and sofosbuvir. They achieved SVR rate of 95.3%; there were no differences in SVR between the 8-week and 12-week cohorts. No differences were observed in SVR across genotype subtype or fibrosis stage.

“In this real-world experience of HCV treatment in genotype1 treatment-naïve patients, high SVR rates, comparable to that was observed in registration trials,” said Younossi.

Previous studies have shown higher rates of virological relapse in genotype 1a patients after 8 weeks of treatment. But in this real-world cohort, “very low or no difference was observed in relapse rates across genotype subtype and treatment duration,” Yousonni said.

The study has some limitations. Treating physicians had discretion over treatment duration, which led to significantly more patients older than 65 years, men, diabetics and more advanced fibrosis patients in the cohort treated for 12 weeks. The entire cohort included some patients who did not have a formal assessment of liver fibrosis as well as patients who had platelet count of <100 000/μL.

To more stringently evaluate the efficacy of the ledipasvir/sofosbuvir combination for 8 weeks versus 12 weeks in true non-cirrhotic patients, the researchers further analyzed the SVR rates in a cohort with formal assessment of liver fibrosis, platelet count of >100 000/μL and an APRI of >1.0. They found excellent SVR rates of 97% in the 8-week and 12-weeks cohorts.

The study supports the FDA recommendation that “clinicians should consider 8 weeks of ledipasvir/sofosbuvir for initial treatment of HCV genotype 1, treatment-naïve, non-cirrhotic patients,” concluded Younossi.