In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.
BACKGROUND
Peginterferon–ribavirin therapy is the current standard of
care for chronic infection with hepatitis C virus (HCV). The rate of
sustained virologic response has been below 50% in cases of HCV
genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has
been evaluated as an additional treatment in phase 1 and phase 2
studies.
METHODS
We conducted a double-blind study in which previously untreated
adults with HCV genotype 1 infection were randomly assigned to one of three
groups. In all three groups, peginterferon alfa-2b and ribavirin were
administered for 4 weeks (the leadin period). Subsequently, group 1 (the
control group) received placebo plus peginterferon–ribavirin for 44
weeks; group 2 received boceprevir plus peginterferon–ribavirin for
24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24
received placebo plus peginterferon–ribavirin for an additional 20
weeks; and group 3 received boceprevir plus peginterferon–ribavirin
for 44 weeks. Nonblack patients and black patients were enrolled and
analyzed separately.
RESULTS
A total of 938 nonblack and 159 black patients were treated. In the
nonblack cohort, a sustained virologic response was achieved in 125 of the
311 patients (40%) in group 1, in 211 of the 316 patients
(67%) in group 2 (P<0.001), and in 213 of the 311 patients
(68%) in group 3 (P<0.001). In the black cohort, a sustained
virologic response was achieved in 12 of the 52 patients (23%) in
group 1, in 22 of the 52 patients (42%) in group 2 (P =
0.04), and in 29 of the 55 patients (53%) in group 3 (P =
0.004). In group 2, a total of 44% of patients received
peginterferon–ribavirin for 28 weeks. Anemia led to dose reductions
in 13% of controls and 21% of boceprevir recipients, with
discontinuations in 1% and 2%, respectively.
CONCLUSIONS
The addition of boceprevir to standard therapy with
peginterferon–ribavirin, as compared with standard therapy alone,
significantly increased the rates of sustained virologic response in
previously untreated adults with chronic HCV genotype 1 infection. The rates
were similar with 24 weeks and 44 weeks of boceprevir. (Funded by
Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov
number, NCT00705432.)
In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.).
Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).
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. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330.).
Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients infected with HCV genotype 1, 2, or 3, including patients with no response to prior therapy with telaprevir or boceprevir. (Funded by Bristol-Myers Squibb and Pharmasset (Gilead); A1444040 ClinicalTrials.gov number, NCT01359644.).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.