Page 16 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
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of ritonavir-boosted paritaprevir, ombitasvir and dasabuvir plus JOURNAL OF HEPATOLOGY
ribavirin in the TURQUOISE-II trial. SVR12 was achieved in 92%
(239/261) of genotype 1a and 99% (118/119) of genotype 1b SVR12 in 88% (68/88) of treatment-naïve non-cirrhotic and 75%
(41/55) of treatment-naïve cirrhotic patients; SVR rates were
patients [45]. In patients with a-fetoprotein level <20 ng/ml, plate- 87% (64/74) and 76% (53/70) in treatment-experienced non-cir-
rhotic and cirrhotic patients, respectively (intent-to-treat) [28].
let count P90 Â 109/L and albumin level P35 g/L prior to treat-
ment, the relapse rates were 1% (1/87) and 0% (0/68) after 12 or Genotype 1, IFN-free Option 4
24 weeks of treatment, respectively; in patients with a-fetopro- • Patients infected with HCV genotype 1 can be treated
with an IFN-free combination of daily sofosbuvir (400
tein level P20 ng/ml and/or platelet count <90 Â 109/L and/or mg) and daily daclatasvir (60 mg) for 12 weeks (A1)
albumin level <35 g/L prior to treatment, they were 21% (10/48)
and 2% (1/45) after 12 or 24 weeks of treatment, respectively [45]. • Based on data with other IFN-free combinations,
adding daily weight-based ribavirin (1000 or 1200
Genotype 1, IFN-free Option 3 mg in patients <75 kg or ≥75 kg, respectively) is
recommended in patients with cirrhosis (B1)
• Patients infected with HCV genotype 1 can be treated
with an IFN-free combination of daily sofosbuvir (400 • In patients with cirrhosis with contra-indications to the
mg) and daily simeprevir (150 mg) for 12 weeks (A1) use of ribavirin, extending duration of treatment to 24
weeks must be considered (B1)
• Based on data with other IFN-free combinations,
adding daily weight-based ribavirin (1000 or 1200 Comments: Phase IIb results have been published with this com-
mg in patients <75 kg or ≥75 kg, respectively) is bination in patients without cirrhosis [14]. With 24 weeks of
recommended in patients with cirrhosis (B1) therapy, the SVR rates were 100% (14/14 and 15/15, without
and with ribavirin, respectively) in treatment-naïve patients,
• In patients with cirrhosis with contra-indications to the and 100% (21/21) and 95% (19/21) without and with ribavirin,
use of ribavirin, extending duration of treatment to 24 respectively, in patients who did not respond to the combination
weeks must be considered (B1)
of PegIFN-a, ribavirin, and either telaprevir or boceprevir. With
Comments: This recommendation is based on results from the
COSMOS Phase IIb trial [11]. In the first cohort, 80 prior null 12 weeks of therapy, SVR was achieved in 98% (40/41) of treat-
ment-naïve patients without ribavirin (the remaining patient
responders to PegIFN-a and ribavirin therapy with a METAVIR was lost to follow-up) [14]. Large-scale real-life data from
European early access programmes will be presented in 2015.
score F0 to F2 were treated 12 or 24 weeks, with or without rib-
avirin. The SVR12 rates were 93% (13/14) and 96% (26/27) for Treatment of HCV genotype 2 infection
12 weeks of therapy without and with ribavirin, respectively,
and 93% (14/15) and 79% (19/24) for 24 weeks of therapy without The best first-line treatment option for patients infected with
and with ribavirin, respectively. In the second cohort, 87 treat- HCV genotype 2 is the IFN-free combination of sofosbuvir and
ment-naïve patients and prior null responders with a METAVIR ribavirin. Other options may be useful in the small number of
score of F3–F4 were treated 12 or 24 weeks, without or with patients who fail on this regimen. In settings where these options
ribavirin. The SVR12 rates were 93% (13/14) and 93% (25/27)
for 12 weeks of therapy without and with ribavirin, respectively, are not available, the combination of PegIFN-a and ribavirin
and 100% (16/16) and 93% (28/30) for 24 weeks of therapy with-
out and with ribavirin, respectively. All virological failures were remains acceptable, according to previously published EASL
due to post-treatment relapses [11]. Clinical Practice Guidelines [5].
Preliminary results from two large-scale US real-life studies Genotype 2, Option 1
with sofosbuvir and simeprevir indicate that this combination is
well tolerated and yields high SVR rates, which are however lower • Patients infected with HCV genotype 2 must be treated
than those reported in the COSMOS trial, in particular in patients with daily weight-based ribavirin (1000 or 1200 mg
with advanced stages of liver disease [13,28]. These studies are in patients <75 kg or ≥75 kg, respectively), and daily
not conclusive as to the value of adding ribavirin to the sofosbu- sofosbuvir (400 mg) for 12 weeks (A1)
vir-simeprevir combination (ribavirin addition was at the pre-
scriber’s discretion and may have been influenced by various • Therapy should be prolonged to 16 or 20 weeks in
pretreatment parameters). In HCV TARGET 2.0 [13], the overall patients with cirrhosis, especially if they are treatment-
SVR4 rate was 89% (269/303). SVR4 was achieved in 92% (113/ experienced (B1)
123) of non-cirrhotic patients, 87% (156/180) of cirrhotic patients,
and 75% (61/81) of cirrhotic patients with prior decompensation. Comments: Results from four Phase III trials have been pub-
SVR4 was more frequent in subtype 1b than 1a patients: 95% lished. In the FISSION trial in treatment-naïve patients treated
(88/93) and 89% (47/53), respectively. SVR4 was achieved in 81% 12 weeks [25], the SVR rate was 95% (69/73). The response rate
(44/54) of patients who failed on a prior treatment with PegIFN- was better in patients without cirrhosis (97% vs. 83% in patients
a, ribavirin and either telaprevir or boceprevir, including in 85% 15
(17/20) of non-cirrhotic patients and 79% (27/34) of cirrhotic
patients. Preliminary data from the TRIO real-life study showed
ribavirin in the TURQUOISE-II trial. SVR12 was achieved in 92%
(239/261) of genotype 1a and 99% (118/119) of genotype 1b SVR12 in 88% (68/88) of treatment-naïve non-cirrhotic and 75%
(41/55) of treatment-naïve cirrhotic patients; SVR rates were
patients [45]. In patients with a-fetoprotein level <20 ng/ml, plate- 87% (64/74) and 76% (53/70) in treatment-experienced non-cir-
rhotic and cirrhotic patients, respectively (intent-to-treat) [28].
let count P90 Â 109/L and albumin level P35 g/L prior to treat-
ment, the relapse rates were 1% (1/87) and 0% (0/68) after 12 or Genotype 1, IFN-free Option 4
24 weeks of treatment, respectively; in patients with a-fetopro- • Patients infected with HCV genotype 1 can be treated
with an IFN-free combination of daily sofosbuvir (400
tein level P20 ng/ml and/or platelet count <90 Â 109/L and/or mg) and daily daclatasvir (60 mg) for 12 weeks (A1)
albumin level <35 g/L prior to treatment, they were 21% (10/48)
and 2% (1/45) after 12 or 24 weeks of treatment, respectively [45]. • Based on data with other IFN-free combinations,
adding daily weight-based ribavirin (1000 or 1200
Genotype 1, IFN-free Option 3 mg in patients <75 kg or ≥75 kg, respectively) is
recommended in patients with cirrhosis (B1)
• Patients infected with HCV genotype 1 can be treated
with an IFN-free combination of daily sofosbuvir (400 • In patients with cirrhosis with contra-indications to the
mg) and daily simeprevir (150 mg) for 12 weeks (A1) use of ribavirin, extending duration of treatment to 24
weeks must be considered (B1)
• Based on data with other IFN-free combinations,
adding daily weight-based ribavirin (1000 or 1200 Comments: Phase IIb results have been published with this com-
mg in patients <75 kg or ≥75 kg, respectively) is bination in patients without cirrhosis [14]. With 24 weeks of
recommended in patients with cirrhosis (B1) therapy, the SVR rates were 100% (14/14 and 15/15, without
and with ribavirin, respectively) in treatment-naïve patients,
• In patients with cirrhosis with contra-indications to the and 100% (21/21) and 95% (19/21) without and with ribavirin,
use of ribavirin, extending duration of treatment to 24 respectively, in patients who did not respond to the combination
weeks must be considered (B1)
of PegIFN-a, ribavirin, and either telaprevir or boceprevir. With
Comments: This recommendation is based on results from the
COSMOS Phase IIb trial [11]. In the first cohort, 80 prior null 12 weeks of therapy, SVR was achieved in 98% (40/41) of treat-
ment-naïve patients without ribavirin (the remaining patient
responders to PegIFN-a and ribavirin therapy with a METAVIR was lost to follow-up) [14]. Large-scale real-life data from
European early access programmes will be presented in 2015.
score F0 to F2 were treated 12 or 24 weeks, with or without rib-
avirin. The SVR12 rates were 93% (13/14) and 96% (26/27) for Treatment of HCV genotype 2 infection
12 weeks of therapy without and with ribavirin, respectively,
and 93% (14/15) and 79% (19/24) for 24 weeks of therapy without The best first-line treatment option for patients infected with
and with ribavirin, respectively. In the second cohort, 87 treat- HCV genotype 2 is the IFN-free combination of sofosbuvir and
ment-naïve patients and prior null responders with a METAVIR ribavirin. Other options may be useful in the small number of
score of F3–F4 were treated 12 or 24 weeks, without or with patients who fail on this regimen. In settings where these options
ribavirin. The SVR12 rates were 93% (13/14) and 93% (25/27)
for 12 weeks of therapy without and with ribavirin, respectively, are not available, the combination of PegIFN-a and ribavirin
and 100% (16/16) and 93% (28/30) for 24 weeks of therapy with-
out and with ribavirin, respectively. All virological failures were remains acceptable, according to previously published EASL
due to post-treatment relapses [11]. Clinical Practice Guidelines [5].
Preliminary results from two large-scale US real-life studies Genotype 2, Option 1
with sofosbuvir and simeprevir indicate that this combination is
well tolerated and yields high SVR rates, which are however lower • Patients infected with HCV genotype 2 must be treated
than those reported in the COSMOS trial, in particular in patients with daily weight-based ribavirin (1000 or 1200 mg
with advanced stages of liver disease [13,28]. These studies are in patients <75 kg or ≥75 kg, respectively), and daily
not conclusive as to the value of adding ribavirin to the sofosbu- sofosbuvir (400 mg) for 12 weeks (A1)
vir-simeprevir combination (ribavirin addition was at the pre-
scriber’s discretion and may have been influenced by various • Therapy should be prolonged to 16 or 20 weeks in
pretreatment parameters). In HCV TARGET 2.0 [13], the overall patients with cirrhosis, especially if they are treatment-
SVR4 rate was 89% (269/303). SVR4 was achieved in 92% (113/ experienced (B1)
123) of non-cirrhotic patients, 87% (156/180) of cirrhotic patients,
and 75% (61/81) of cirrhotic patients with prior decompensation. Comments: Results from four Phase III trials have been pub-
SVR4 was more frequent in subtype 1b than 1a patients: 95% lished. In the FISSION trial in treatment-naïve patients treated
(88/93) and 89% (47/53), respectively. SVR4 was achieved in 81% 12 weeks [25], the SVR rate was 95% (69/73). The response rate
(44/54) of patients who failed on a prior treatment with PegIFN- was better in patients without cirrhosis (97% vs. 83% in patients
a, ribavirin and either telaprevir or boceprevir, including in 85% 15
(17/20) of non-cirrhotic patients and 79% (27/34) of cirrhotic
patients. Preliminary data from the TRIO real-life study showed
