A two-drug regimen of sofosbuvir (Sovaldi) and ribavirin taken for 12 weeks led to sustained
virological response in all treated adolescents with hepatitis C virus (HCV)
genotype 2, while a 24-week course cured all but one teen with harder-to-treat
genotype 3, according to a presentation at the 2017 Pediatric Academic Societies Meeting last week
in San Francisco.
Experts estimate that
up to 0.4% of children in the US and Europe, and up to 6% in resource-limited
countries such as Egypt, are living with hepatitis C, mostly attributable to
mother-to-child transmission.
The advent of
direct-acting antivirals (DAAs) used in interferon-free regimens has
transformed treatment of chronic hepatitis C, but the new drugs have not been
extensively tested in adolescents or children, and until recently interferon-based
therapy remained the standard of care for paediatric patients.
Regino Gonzalez-Peralta of the University of Florida in Gainesville and
colleagues evaluated sofosbuvir plus ribavirin for adolescents age 12 to 17
with HCV genotypes 2 or 3, which are less common in the US but are a major
public health problem in parts of Africa, Asia, and the Middle East.
The study enrolled 50 adolescents with chronic
hepatitis C (average age 15 years) in the US, UK, Europe, Russia, Australia and
New Zealand; 13 had genotype 2 and 37 had genotype 3. None of the adolescents with genotype 2 had been previously treated for hepatitis C, but 24% in the
genotype 3 group were treatment-experienced. None were known to have liver
cirrhosis, but 60% had unknown disease status.
Participants with HCV genotype 2 in this open-label
study were treated with once-daily sofosbuvir (400mg) plus ribavirin (15 mg/kg/day) for 12 weeks.
Those with genotype 3 received the same combination for 24 weeks. The
first 10 teens were included in a pharmacokinetic substudy, which showed that
plasma drug concentrations were comparable to those seen in adults.
The overall rate of sustained virological response –
or undetectable HCV RNA at 12 weeks post-treatment (SVR12) – was 98% in an
intent-to-treat analysis. SVR12 rates were 100% for the genotype 2 group and
97% for the genotype 3 group. One individual with genotype 3 was lost to follow-up
at four weeks post-treatment, but had undetectable HCV RNA at that time.
Treatment was generally safe and well tolerated. There
were no serious adverse events and no early discontinuations for this reason.
The most common adverse events were headache and nausea. While 19% of teens in
the 24-week treatment group – but none in the 12-week group – had grade 3-4 laboratory
abnormalities, mostly transient drops in haemoglobin, none of them developed anaemia
using haemoglobin cut-offs below 8.5 or 10 g/dl.
"Sofosbuvir plus ribavirin represents an
important treatment option for adolescents with chronic HCV genotype 2 or 3
infection," the
researchers concluded.
While these study results look good, hepatitis C drug
approvals have moved faster than research can be completed, and this is already
considered an obsolete regimen for adults.
In April the US Food and Drug Administration approved sofosbuvir plus ribavirin
for adolescents with HCV genotypes 2 or 3, and the sofosbuvir/ledipasvir
co-formulation (Harvoni) for those
with genotypes 1, 4, 5 or 6.
A study presented at the 2016 EASL International Liver
Congress showed that sofosbuvir/ledipasvir is highly effective for adolescents age 12 to 17 with genotype
1. Another study at this year's EASL meeting showed that this combination also worked well for younger children age 6 to 11.
As with Gonzalez-Peralta's study, most of the participants in these trials
did not have confirmed liver cirrhosis, though many had not been evaluated for
it.
A related study presented at the Pediatric Academic Society Meeting described a
case series of adolescents with cirrhosis who were treated with sofosbuvir/ledipasvir
as part of a compassionate use programme prior to its approval.
Kristina Reed of the University of Oklahoma Health Sciences Center reported on three teens with
HCV genotype 1a who did not respond to pegylated interferon and ribavirin. All had
biopsy-proven cirrhosis. They all achieved SVR and no longer required liver
transplants.
The current AASLD HCV treatment guidelines and EASL
guidelines no longer recommend sofosbuvir plus
ribavirin for adults, even those with easy-to-treat genotype 2. Instead they
recommend sofosbuvir plus daclatasvir (Daklinza)
or the pangenotypic sofosbuvir/velpatasvir co-formulation (Epclusa).
Gonzalez-Peralta acknowledged
that a regimen containing two DAAs may be a better option for teens. A study of
sofosbuvir/velpatasvir for adolescents is now underway.