People on opiate substitution therapy can be
successfully treated with grazoprevir/elbasvir (Zepatier), leading to improvements in some aspects of quality of
life, according to findings from the C-EDGE CO-STAR study presented at the 2016 International Liver Congress last month in Barcelona. However, the same study saw several cases of
hepatitis C virus (HCV) reinfection after a cure, suggesting a greater emphasis
on prevention may be warranted.
HCV is easily transmitted through shared drug
injection equipment, and current and former injection drug users have high
rates of infection. However, some providers and insurers still consider people
who inject drugs (PWID) to be poor candidates for hepatitis C treatment and
active drug users have been excluded from most trials of direct-acting
Gregory Dore from the Kirby Institute at the
University of New South Wales and colleagues conducted the phase 3 C-EDGE
CO-STAR trial to evaluate Merck's HCV NS3/4A protease inhibitor grazoprevir and
HCV NS5A inhibitor elbasvir for PWID receiving opioid agonist substitution
therapy using methadone or buprenorphine. The grazoprevir/elbasvir
co-formulation previously demonstrated cure rates of 90% or better in non-PWID
CO-STAR enrolled 301 previously untreated people with
HCV genotypes 1, 4 or 6. About three-quarters were men, the median age was 48
years, 20% had liver cirrhosis and 8% had HIV/HCV co-infection. Participants
were required to be on stable opioid agonist therapy (mostly methadone) for at
least three months. They were randomly assigned to receive either
grazoprevir/elbasvir or placebo once daily for 12 weeks, at which point the
study was unblinded and placebo recipients were also given active treatment on
an open-label basis.
As Prof Dore reported at the 2015 AASLD Liver
Meeting last November, the overall sustained virological
response rate at 12 weeks post-treatment (SVR12) for people randomised to
grazoprevir/elbasvir was 92%, rising to 96% in a modified population that excluded people who discontinued the study for
non-treatment-related reasons or became reinfected after HCV clearance. Treatment
was generally safe and well tolerated. Urine screens showed that
non-prescription drug use continued throughout the study.
In a poster at the EASL meeting Dore's team reported results from an
exploratory analysis looking at the impact of hepatitis C treatment on
health-related quality of life (HRQoL).
Health-related quality of life was assessed
using the SF-36v2
health survey, which participants completed on their own at baseline, at
treatment week 4, at the end of treatment at week 12 and at post-treatment
follow-up weeks 4 and 12. Researchers looked at eight health domain scores, and
individual domain scores were used to calculate physical component summary and
mental component summary scores.
Almost all participants (98%) in both the
grazoprevir/elbasvir and placebo groups completed the baseline and at least one
follow-up HRQoL assessment. At baseline mean HRQoL scores were comparable
between the two groups.
During treatment there were no significant mean improvements
within each treatment group in the eight health domains or in the physical or
mental summary scores during treatment. In general, mean changes in HRQoL
score were more favourable in the grazoprevir/elbasvir group than in the
placebo group, but there were no significant differences in mean change scores
between the groups at treatment week 12.
At post-treatment follow-up week 4, the
grazoprevir/elbasvir group saw significant improvements from baseline in two
domains – general health and vitality – while the placebo group saw a decline
in the mental health domain. Again, mean changes were generally more favourable
in the grazoprevir/elbasvir group than in the placebo group, and at this point
significant differences in mean change scores were noted, with the
grazoprevir/elbasvir group seeing more improvement in general health, vitality,
mental health and mental component summary scores.
However, in the final assessment at follow-up week 12,
only the general health score showed significant improvement in the
The researchers noted that HRQoL scores among
participants in this study were lower than those observed in studies of
grazoprevir/elbasvir in people with hepatitis C who did not inject drugs. This
lower health-related quality of life may be due to the high rates of co-morbidities
among CO-STAR participants or to ongoing drug use, they suggested.