Prescrire International Special Edition 2015/Volume 24 N°158
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•
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age
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Translated from
Rev Prescrire
October 2014; 34 (372): 726-732
sofosbuvir
(S
ovaldi
°)
Active against hepatitis C virus, but evaluation is incomplete
About 50% of patients with chronic
hepatitis C virus (HCV) genotype 1
infection have a sustained virological
response to a 48-week course of the
peginterferon alfa
+
ribavirin
combi-
nation. Adding a viral protease inhi-
bitor to this combination for 12 to
32 weeks enhances antiviral effects
but increases the risk of serious
adverse effects.
Between 70% and 80% of patients
with HCV genotype 2 or 3 infection
have a sustained virological response
to a 24-week course of the
peginter-
feron alfa
+
ribavirin
combination.
Sofosbuvir
, a nucleotide inhibitor
of viral (or HCV) NS5B RNA polymer-
ase, has been authorised in the Euro-
pean Union for the treatment of chron-
ic hepatitis C, in combination with
other drugs. Despite the inclusion of
several clinical trials, initial evaluation
of
sofosbuvir
provides only a minimal
picture of the harm-benefit balance.
Sofosbuvir
has not been compared
directly with viral protease inhibitors
in randomised clinical trials.
In a trial involving 121 patients with
HCV genotype 1 infection, the sus-
tained viral response rate was 90%
when
sofosbuvir
was added to the
peginterferonalfa
+
ribavirin
combination
for 12 weeks, versus about 60% with
peginterferon alfa
+
ribavirin
alone.
In a randomised, unblinded, non-
inferiority trial in 527 previously
untreated patients with HCV geno-
type 2 or 3 infection,
sofosbuvir
+
riba-
virin
combination therapy given for
12 weeks had virological efficacy
similar to
peginterferon alfa
-2a +
riba-
virin
combination therapy given for
24 weeks. However, there were signs
that
sofosbuvir
might be less effective
against HCV genotype 3.
In an uncontrolled study of
114 patients with HCV genotype 1
infection who could not receive
peg-
interferon alfa
, the
sofosbuvir
+ riba
virin
combination yielded sustained
virological responses in about 75% of
cases. Similar results were obtained
in a double-blind, placebo-controlled
trial in 280 patients with HCV geno-
type 2 or 3 infection.
Too few cases of HCV genotype
4, 5 or 6 infection were included in
clinical trials to determine the value
of
sofosbuvir
in these patients.
The adverse effects of
sofos-
buvir
are poorly documented, main-
ly because of the limited number of
patients in clinical trials and the lack
of blinding in several trials. In particu-
lar, more data are needed on possible
effects on the heart, blood cells and
muscle.
Renal failure can lead to
sofosbuvir
overdose, while co-administration of
P‑glycoprotein inhibitors can lead to
sofosbuvir
underdosing.
There are no data available on the
use of
sofosbuvir
in pregnant women.
Contraception is necessary when
sofosbuvir
is used in combination
with
ribavirin
because the latter drug
is teratogenic, potentially for several
months after treatment discontinua-
tion.
When HCV liver disease warrants
medical treatment,
sofosbuvir
seems
to be at least as effective as viral pro-
tease inhibitors such as
boceprevir
,
and also less toxic. Its use can shorten
treatment duration by several months.
There are many uncertainties, how-
ever, about its adverse effects and drug
interactions. Adding
sofosbuvir
to the
peginterferon alfa
+
ribavirin
combi-
nation is an option for patients with
genotype 1 infection, while
sofosbuvir
is an alternative to
peginterferon alfa
for patients with genotype 2 or 3 infec-
tion. Waiting for more thorough evalu-
ation is another reasonable option,
depending on clinical status, given
the slow progression of hepatitis C
and the many outstanding questions
concerning
sofosbuvir
.
sofosbuvir
tablets
S
ovaldi
°
• 400 mg
of
sofosbuvir
per tablet
antiviral agent; NS5B
polymerase inhibitor
Indication:
“(…) in combination with
other medicinal products for the treatment
of chronic hepatitis C (CHC) in adults”.
[EU marketing authorisation, centralised
procedure]
OFFERS AN ADVANTAGE
In patients with chron-
ic hepatitis due to
hepa-titis C virus
(HCV) genotype 1,
adding
sofosbuvir
to
the
peginterferon alfa
+
ribavirin
combination seems to be at least
as effective as adding
boceprevir
.
Sofosbuvir
appears to be less toxic
than
boceprevir
.
The
sofosbuvir
+
ribavirin
combi-
nation is not more effective viro-
logically than the
peginterferon
alfa
+
ribavirin
combination on HCV
genotype 2 or 3 infection, but it
may have fewer adverse effects.
Sofosbuvir
represents an alterna-
tive to
peginterferon alfa
for these
patients. The specific adverse
effects of
sofosbuvir
are poorly
documented. Few serious adverse
effects have been described, but
more data are needed on possible
cardiac, haematological, and mus-
cular adverse effects.
Rev Prescrire
2014; 34 (372): 726-732.
Abstract
Prescrire Int • January 2015
