High rates of sustained virologic response were observed among patients with hepatitis C virus ( HCV ) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor Sofosbuvir combined with the NS5A inhibitor Ledipasvir. This study examined 8 weeks of treatment with this regimen.
In this phase 3, open-label study, researchers have randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive Ledipasvir and Sofosbuvir ( Ledipasvir-Sofosbuvir ) for 8 weeks, Ledipasvir - Sofosbuvir plus Ribavirin for 8 weeks, or Ledipasvir - Sofosbuvir for 12 weeks.
The primary end point was sustained virologic response at 12 weeks after the end of therapy.
The rate of sustained virologic response was 94% ( 95% confidence interval [CI], 90 to 97 ) with 8 weeks of Ledipasvir - Sofosbuvir, 93% ( 95% CI, 89 to 96 ) with 8 weeks of Ledipasvir - Sofosbuvir plus Ribavirin, and 95% ( 95% CI, 92 to 98 ) with 12 weeks of Ledipasvir - Sofosbuvir.
As compared with the rate of sustained virologic response in the group that received 8 weeks of Ledipasvir -Sofosbuvir, the rate in the 12-week group was 1 percentage point higher ( 97.5% CI, −4 to 6 ) and the rate in the group that received 8 weeks of Ledipasvir - Sofosbuvir with Ribavirin was 1 percentage point lower ( 95% CI, −6 to 4 ); these results have indicated noninferiority of the 8-week Ledipasvir - Sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points.
Adverse events were more common in the group that received Ribavirin than in the other two groups.
No patient who has received 8 weeks of only Ledipasvir - Sofosbuvir discontinued treatment owing to adverse events.
In conclusion, Ledipasvir - Sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis.
No additional benefit was associated with the inclusion of Ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. ( Xagena )
Kowdley KV et al, NEJM 2014; Epub ahead of print