Currently available triple therapies for
hepatitis C carry a high risk of serious side-effects for people in the most
urgent need of treatment, and these patients have only a moderate chance of
being cured, according to the findings of studies of telaprevir and boceprevir treatment
in people with cirrhosis at liver centres in France and Austria reported last week
at the 48th International Liver Congress (EASL 2013) in Amsterdam.
Due to the high risk of progression from
compensated cirrhosis to decompensated cirrhosis, people
with hepatitis C virus (HCV) and cirrhosis have a more urgent need for treatment. However,
clinical trials of HCV protease inhibitors provided limited information about
the effects of these drugs in people with cirrhosis.
The hepatitis C protease inhibitors
telaprevir (Incivo) and boceprevir (Victrelis) were made available through
an early access programme in France prior to licensing in 2011, for people who
could not obtain access to the drugs in phase III clinical trials.
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
- compensated cirrhosis
The earlier stage of
cirrhosis, during which the liver is damaged but still able to perform most of
its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
A disease or infection affecting the brain.
A natural hormone made in the kidneys to stimulate the production of red blood cells by the bone marrow.
The presence of pus-forming bacteria in the body.
The Compassionate Use of Protease
Inhibitors in Cirrhotics (CUPIC) cohort study was the first to collect
data on the use of protease inhibitors in triple therapy for people with
cirrhosis who had failed to respond to interferon-based therapy.
Previous results from the cohort were presented
at the International Liver Congress in 2012 and at the American
Liver Meeting in 2012. (Read more about the background to this study by
following the links). The study showed a high rate of serious side-effects.
Investigators concluded that people with cirrhosis required careful
The findings presented at the 2013
International Liver Congress provide an update on the outcomes of 221 people
who have been followed for at least 60 weeks after starting treatment.
The study population comprised people with
compensated cirrhosis, all of whom had HCV genotype-1.
Participants received triple-drug HCV
therapy incorporating one of the approved protease inhibitors boceprevir(Victrelis) or telaprevir (Incivo).
Telaprevir-based therapy was provided
according to the following protocol:
- Phase 1 (12 weeks): telaprevir
with pegylated interferon-2a and ribavirin.
- Phase 2 (36 weeks): pegylated
interferon and ribavirin.
The regimen for the boceprevir-treated
patients consisted of a four-week lead-in phase of pegylated interferon and
ribavirin after which boceprevir was added. Treatment lasted for a further 44
All patients had been treated previously.
Approximately 40% in each group had achieved a prior partial response to
treatment, and around 45% had experienced virologic relapse. Five per cent in
the boceprevir group and ten per cent in the telaprevir group were prior null
Interim analysis of outcomes in 221
patients who reached 60 weeks of follow-up showed that 41% of individuals
treated with boceprevir and 40% of those receiving telaprevir had a sustained
virological response (SVR) twelve weeks after completing therapy. SVR rates
differed according to the outcome of earlier HCV therapy. They were highest for
patients who had relapsed (boceprevir, 51%; telaprevir, 53%), followed by individuals
with a partial response (boceprevir, 40%; telaprevir, 32%) and null responders
(boceprevir, 11%; telaprevir, 29%). Multivariate analysis showed that prior
relapsers were twice as likely to achieve SVR12 when compared to partial or
null responders (odds ratio 2.03).
Cure rates were significantly better in
genotype 1b infection (51% boceprevir; 46% telaprevir) than in genotype 1a
infection (boceprevir 31%; telaprevir 34%). Multivariate analysis showed that
patients with genotype 1b were almost twice as likely to achieve SVR 12 (odds
Serious adverse events were observed in 54%
of patients treated with telaprevir and 51% of individuals receiving
boceprevir. Discontinuation rates due to adverse events were somewhat higher in people taking telaprevir (boceprevir, 11%; telaprevir, 21%). Five per cent
of people taking telaprevir developed grade 3 (serious) rash and two
patients suffered severe cutaneous adverse reaction (SCAR), a potentially
life-threatening form of rash which produces systemic symptoms. Severe rash
also occurred in 1% of boceprevir recipients.
There was a 2.4% mortality rate among the
telaprevir-treated patients and 1.6% of individuals receiving boceprevir also
died. Causes of death were not reported.mostly related to infections: In the
telaprevir group, there were seven deaths. Three patients died of sepsis (blood
poisoning) and another one of pneumonia (lung inflammation). Three further
patients died because of variceal bleeding, or encephalopathy, or pulmonary neoplasia . In the boceprevir group there
were three deaths, one due to pneumonia, another to sepsis and one to
The incidence of serious grade 3 or 4 infections was 7% for
telaprevir and 4.2% for boceprevir.
Liver decompensation was diagnosed in 5.1% of
telaprevir-treated patients and 4.7% of individuals treated with boceprevir.
Erythropoietin (EPO) or blood transfusions
were frequently required because of anemia. 168 telaprevir patients required EPO (56.9%) and
53 received blood transfusions (18%). Among those receiving boceprevir, 119
patients (62.6%) received EPO and 26 (13.7%) received blood transfusions.
Outcomes were broadly similar to those
observed among the sub-group of patients with advanced fibrosis or cirrhosis
enrolled in the phase 3 studies that led to the approval of these protease
inhibitors. However the rate of serious adverse events in this “real world”
cohort was higher.