Page 13 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 13
Clinical Practice Guidelines 82) of patients with F3, and 60% (29/48) of patients with F4 (cir-
rhosis). However, for patients who received 24 weeks of treat-
ribavirin and either telaprevir or boceprevir treatment. The SVR12 ment, the SVR rate was lower in those with detectable than in
those with undetectable HCV RNA at treatment week 4 (69% vs.
rate with the triple combination of PegIFN-a, ribavirin and sofos- 93%, respectively) [29,30]. In treatment-naïve, HIV-coinfected
patients receiving this treatment regimen, SVR was achieved in
buvir was 74% in patients who failed to achieve an SVR after receiv- 79% of patients (42/53) [31].
ing PegIFN-a, ribavirin and an investigational protease inhibitor In monoinfected patients who previously relapsed to IFN-a/
alone or in combination with a non-nucleoside inhibitor of the ribavirin-based therapy, SVR24 was achieved in 86% (128/149)
HCV RNA-dependent RNA polymerase or ledipasvir [27]. There is of subtype 1b patients and in 70% (78/111) of subtype 1a
no data with this combination in HIV-coinfected patients, and rela- patients. Among patients infected with genotype 1a, SVR24 was
tively small numbers of patients with cirrhosis were included. achieved in 78% of those without and 47% of those with a detect-
Whether longer treatment duration would be needed in the most able Q80K substitution at baseline [32]. The SVR rate in HIV-coin-
difficult-to-cure population is unknown. fected relapsers was 87% (13/15) in another study [31].
Preliminary results from two large-scale US real-life studies In the ATTAIN Phase III study, SVR12 was achieved in 70%
have been presented. In HCV TARGET 2.0 [13], the overall SVR4 rate (101/145) of prior partial responders and 44% (102/234) of null
with the triple combination of PegIFN-a, ribavirin and sofosbuvir responders to IFN-a/ribavirin-based therapy treated with the tri-
ple combination of PegIFN-a, ribavirin and simeprevir, vs. 68%
was 85% (140/164; 55% were treatment-naïve and 45% treat-
ment-experienced patients). SVR4 was achieved in 90% (114/ (100/146) and 46% (110/238) of the same groups who received
127) of non-cirrhotic patients but 70% (26/37) of cirrhotic patients. telaprevir, respectively [33]. In HIV-coinfected patients, 70% (7/
In the TRIO real-life study, which included 58% of treatment-naïve 10) of partial responders and 54% (15/28) of null responders
and 42% of treatment-experienced patients, SVR12 was achieved in achieved an SVR24 in another study [31].
81% (112/138) of treatment-naïve non-cirrhotic patients and 81%
(25/31) of treatment-naïve cirrhotic patients, and in 77% (30/39) IFN-free options
of treatment-experienced patients without cirrhosis and 62%
(53/85) of treatment-experienced patients with cirrhosis (intent- Genotype 1, IFN-free Option 1
to-treat) receiving PegIFN-a, ribavirin and sofosbuvir [28]. • Patients infected with HCV genotype 1 can be treated
with the IFN-free fixed-dose combination of sofosbuvir
Genotype 1, IFN-containing Option 2 (400 mg) and ledipasvir (90 mg) in a single tablet
administered once daily (A1)
• Patients infected with HCV genotype 1 can be treated
with a combination of weekly PegIFN-α, daily weight- • Patients without cirrhosis, including treatment-naïve
based ribavirin (1000 or 1200 mg in patients <75 kg or and treatment-experienced patients, should be treated
≥75 kg, respectively), and daily simeprevir (150 mg) with this fixed-dose combination for 12 weeks without
(A1) ribavirin (A1)
• This combination is not recommended in patients • Treatment may be shortened to 8 weeks in treatment-
infected with subtype 1a who have a detectable Q80K naïve patients without cirrhosis if their baseline HCV
substitution in the NS3 protease sequence at baseline, RNA level is below 6 million (6.8 Log) IU/ml. This should
as assessed by population sequencing (direct sequence be done with caution, especially in patients with F3
analysis) (A1) fibrosis, pending demonstration of the accuracy of HCV
RNA level determination within this range of values
• Simeprevir should be administered for 12 weeks in and real-life confirmation that 8 weeks of treatment are
combination with PegIFN-α and ribavirin. PegIFN-α sufficient to achieve high SVR rates (B1)
and ribavirin should then be administered alone for an
additional 12 weeks (total treatment duration 24 weeks) • Patients with compensated cirrhosis, including
in treatment-naïve and prior relapser patients, including treatment-naïve and treatment-experienced patients,
cirrhotic patients, and for an additional 36 weeks (total should be treated with this fixed-dose combination for
treatment duration 48 weeks) in prior partial and null 12 weeks with daily weight-based ribavirin (1000 or
responders, including cirrhotic patients (B1) 1200 mg in patients <75 kg or ≥75 kg, respectively) (A1)
• HCV RNA levels should be monitored on treatment. • Patients with compensated cirrhosis with contra-
Treatment should be stopped if HCV RNA level is ≥25 indications to the use of ribavirin or with poor tolerance
IU/ml at treatment week 4, week 12 or week 24 (A2) to ribavirin on treatment should receive the fixed-dose
combination of sofosbuvir and ledipasvir for 24 weeks
Comments: This combination has been evaluated in the QUEST-1 without ribavirin (B1)
and QUEST-2 Phase III clinical trials in treatment-naïve patients
[29,30]. The overall SVR rates were 80% (210/264) and 81% • Treatment with the fixed-dose combination of sofosbuvir
(209/257), respectively. In a pooled analysis of both trials, and ledipasvir with ribavirin can be prolonged to
patients infected with subtype 1b achieved an SVR in 85% of cases 24 weeks in treatment-experienced patients with
(228/267). Patients infected with subtype 1a achieved an SVR in compensated cirrhosis and negative predictors of
84% of cases (138/165) when no Q80K substitution was detect- response, such as a platelet count <75 x 103/μl (B2)
able in the NS3 protease sequence at baseline. The SVR was only
58% (49/84) when a Q80K substitution was detectable at baseline
by population sequencing. SVR was achieved with this regimen in
84% (317/378) of patients with an F0-F2 METAVIR score, 73% (60/
12
rhosis). However, for patients who received 24 weeks of treat-
ribavirin and either telaprevir or boceprevir treatment. The SVR12 ment, the SVR rate was lower in those with detectable than in
those with undetectable HCV RNA at treatment week 4 (69% vs.
rate with the triple combination of PegIFN-a, ribavirin and sofos- 93%, respectively) [29,30]. In treatment-naïve, HIV-coinfected
patients receiving this treatment regimen, SVR was achieved in
buvir was 74% in patients who failed to achieve an SVR after receiv- 79% of patients (42/53) [31].
ing PegIFN-a, ribavirin and an investigational protease inhibitor In monoinfected patients who previously relapsed to IFN-a/
alone or in combination with a non-nucleoside inhibitor of the ribavirin-based therapy, SVR24 was achieved in 86% (128/149)
HCV RNA-dependent RNA polymerase or ledipasvir [27]. There is of subtype 1b patients and in 70% (78/111) of subtype 1a
no data with this combination in HIV-coinfected patients, and rela- patients. Among patients infected with genotype 1a, SVR24 was
tively small numbers of patients with cirrhosis were included. achieved in 78% of those without and 47% of those with a detect-
Whether longer treatment duration would be needed in the most able Q80K substitution at baseline [32]. The SVR rate in HIV-coin-
difficult-to-cure population is unknown. fected relapsers was 87% (13/15) in another study [31].
Preliminary results from two large-scale US real-life studies In the ATTAIN Phase III study, SVR12 was achieved in 70%
have been presented. In HCV TARGET 2.0 [13], the overall SVR4 rate (101/145) of prior partial responders and 44% (102/234) of null
with the triple combination of PegIFN-a, ribavirin and sofosbuvir responders to IFN-a/ribavirin-based therapy treated with the tri-
ple combination of PegIFN-a, ribavirin and simeprevir, vs. 68%
was 85% (140/164; 55% were treatment-naïve and 45% treat-
ment-experienced patients). SVR4 was achieved in 90% (114/ (100/146) and 46% (110/238) of the same groups who received
127) of non-cirrhotic patients but 70% (26/37) of cirrhotic patients. telaprevir, respectively [33]. In HIV-coinfected patients, 70% (7/
In the TRIO real-life study, which included 58% of treatment-naïve 10) of partial responders and 54% (15/28) of null responders
and 42% of treatment-experienced patients, SVR12 was achieved in achieved an SVR24 in another study [31].
81% (112/138) of treatment-naïve non-cirrhotic patients and 81%
(25/31) of treatment-naïve cirrhotic patients, and in 77% (30/39) IFN-free options
of treatment-experienced patients without cirrhosis and 62%
(53/85) of treatment-experienced patients with cirrhosis (intent- Genotype 1, IFN-free Option 1
to-treat) receiving PegIFN-a, ribavirin and sofosbuvir [28]. • Patients infected with HCV genotype 1 can be treated
with the IFN-free fixed-dose combination of sofosbuvir
Genotype 1, IFN-containing Option 2 (400 mg) and ledipasvir (90 mg) in a single tablet
administered once daily (A1)
• Patients infected with HCV genotype 1 can be treated
with a combination of weekly PegIFN-α, daily weight- • Patients without cirrhosis, including treatment-naïve
based ribavirin (1000 or 1200 mg in patients <75 kg or and treatment-experienced patients, should be treated
≥75 kg, respectively), and daily simeprevir (150 mg) with this fixed-dose combination for 12 weeks without
(A1) ribavirin (A1)
• This combination is not recommended in patients • Treatment may be shortened to 8 weeks in treatment-
infected with subtype 1a who have a detectable Q80K naïve patients without cirrhosis if their baseline HCV
substitution in the NS3 protease sequence at baseline, RNA level is below 6 million (6.8 Log) IU/ml. This should
as assessed by population sequencing (direct sequence be done with caution, especially in patients with F3
analysis) (A1) fibrosis, pending demonstration of the accuracy of HCV
RNA level determination within this range of values
• Simeprevir should be administered for 12 weeks in and real-life confirmation that 8 weeks of treatment are
combination with PegIFN-α and ribavirin. PegIFN-α sufficient to achieve high SVR rates (B1)
and ribavirin should then be administered alone for an
additional 12 weeks (total treatment duration 24 weeks) • Patients with compensated cirrhosis, including
in treatment-naïve and prior relapser patients, including treatment-naïve and treatment-experienced patients,
cirrhotic patients, and for an additional 36 weeks (total should be treated with this fixed-dose combination for
treatment duration 48 weeks) in prior partial and null 12 weeks with daily weight-based ribavirin (1000 or
responders, including cirrhotic patients (B1) 1200 mg in patients <75 kg or ≥75 kg, respectively) (A1)
• HCV RNA levels should be monitored on treatment. • Patients with compensated cirrhosis with contra-
Treatment should be stopped if HCV RNA level is ≥25 indications to the use of ribavirin or with poor tolerance
IU/ml at treatment week 4, week 12 or week 24 (A2) to ribavirin on treatment should receive the fixed-dose
combination of sofosbuvir and ledipasvir for 24 weeks
Comments: This combination has been evaluated in the QUEST-1 without ribavirin (B1)
and QUEST-2 Phase III clinical trials in treatment-naïve patients
[29,30]. The overall SVR rates were 80% (210/264) and 81% • Treatment with the fixed-dose combination of sofosbuvir
(209/257), respectively. In a pooled analysis of both trials, and ledipasvir with ribavirin can be prolonged to
patients infected with subtype 1b achieved an SVR in 85% of cases 24 weeks in treatment-experienced patients with
(228/267). Patients infected with subtype 1a achieved an SVR in compensated cirrhosis and negative predictors of
84% of cases (138/165) when no Q80K substitution was detect- response, such as a platelet count <75 x 103/μl (B2)
able in the NS3 protease sequence at baseline. The SVR was only
58% (49/84) when a Q80K substitution was detectable at baseline
by population sequencing. SVR was achieved with this regimen in
84% (317/378) of patients with an F0-F2 METAVIR score, 73% (60/
12
