Nezam Afdhal of Deaconess Medical Center in Boston presented findings
from ION-2, which looked at previously treated patients who did not achieve a
cure with prior interferon-based therapy.
This trial included 440 people living with chronic
hepatitis C in the US. About 65% were men, about 80% were white and
the average age was about 56 years. Nearly 80% had HCV 1a and, as is typical
for prior non-responders, most had unfavourable non-CC IL28B variants. One in
five (20%) had compensated cirrhosis.
About 45% were prior non-responders
who never reached undetectable viral load on prior interferon-based treatment –
a harder group to treat than people who relapsed after finishing treatment.
Half had failed a previous regimen that included one of the first-generation
HCV protease inhibitors – boceprevir (Victrelis)
or telaprevir (Incivek or Incivo) – plus pegylated
interferon/ribavirin.
Again, participants were randomly
assigned to receive the sofosbuvir/ledipasvir coformulation, with or without
ribavirin, for either 12 or 24 weeks.
Here too, SVR12 rates
were high for all treatment arms, and similar to those seen in treatment-naive
patients: 94% with sofosbuvir/ledipasvir for 12
weeks, 96% with sofosbuvir/ledipasvir plus ribavirin for 12 weeks, 99% with
sofosbuvir/ledipasvir for 24 weeks and 99% with sofosbuvir/ledipasvir plus
ribavirin for 24 weeks.
Cure rates in the 12-week
arms were a bit lower for people with cirrhosis: 86% with sofosbuvir/ledipasvir
alone and 82% with sofosbuvir/ledipasvir plus ribavirin. All cirrhotic patients
treated for 24 weeks with either regimen achieved SVR.
There was a single case of
on-treatment viral breakthrough, again in a person with undetectable drug
levels. Among the 14% who had resistance-associated
variants at baseline, 89% still achieved SVR12.
Out of the 11 participants who relapsed,
seven had cirrhosis. Further evaluation of this group did not reveal any specific clinical factors -- such as platelet count
or low albumin -- that predicted who would relapse.
Sofosbuvir/ledipasvir was again
generally well tolerated. Nine patients (2%) had treatment-emergent serious
adverse events, but no one stopped treatment early for this reason. Overall,
adverse events occurred more often in the ribavirin-containing arms. Anaemia
occurred in 5% of ribavirin recipients but none who used sofosbuvir/ledipasvir
alone.
Again, the researchers concluded
that sofosbuvir/ledipasvir was highly effective for treatment-experienced
patients and adding ribavirin or extending treatment duration did not
significantly increase the likelihood of a cure.
Asked whether people with cirrhosis should
be treated for 12 or 24 weeks, Afdhal noted that among the more than 200
cirrhotic patients in the three ION studies, only 4% relapsed.
"We would have to overtreat 9
out of 10 people to get a benefit for extended treatment," he explained.
"It does not make clinical or fiscal sense to overtreat these
patients."