Page 12 - EASL Recommendations on Treatment of Hepatitis C 2015
P. 12
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].
Genotype 1, IFN-containing Option 2
• Patients infected with HCV genotype 1 can be treated • Patients infected with HCV genotype 1 can be treated
with a combination of weekly PegIFN-α, daily weight- with the IFN-free fixed-dose combination of sofosbuvir
based ribavirin (1000 or 1200 mg in patients <75 kg or (400 mg) and ledipasvir (90 mg) in a single tablet
≥75 kg, respectively), and daily simeprevir (150 mg) administered once daily (A1)
(A1)
• Patients without cirrhosis, including treatment-naïve
• This combination is not recommended in patients and treatment-experienced patients, should be treated
infected with subtype 1a who have a detectable Q80K with this fixed-dose combination for 12 weeks without
substitution in the NS3 protease sequence at baseline, ribavirin (A1)
as assessed by population sequencing (direct sequence
analysis) (A1) • Treatment may be shortened to 8 weeks in treatment-
naïve patients without cirrhosis if their baseline HCV
• Simeprevir should be administered for 12 weeks in RNA level is below 6 million (6.8 Log) IU/ml. This should
combination with PegIFN-α and ribavirin. PegIFN-α be done with caution, especially in patients with F3
and ribavirin should then be administered alone for an fibrosis, pending demonstration of the accuracy of HCV
additional 12 weeks (total treatment duration 24 weeks) RNA level determination within this range of values
in treatment-naïve and prior relapser patients, including and real-life confirmation that 8 weeks of treatment are
cirrhotic patients, and for an additional 36 weeks (total sufficient to achieve high SVR rates (B1)
treatment duration 48 weeks) in prior partial and null
responders, including cirrhotic patients (B1) • Patients with compensated cirrhosis, including
treatment-naïve and treatment-experienced patients,
• HCV RNA levels should be monitored on treatment. should be treated with this fixed-dose combination for
Treatment should be stopped if HCV RNA level is ≥25 12 weeks with daily weight-based ribavirin (1000 or
IU/ml at treatment week 4, week 12 or week 24 (A2) 1200 mg in patients <75 kg or ≥75 kg, respectively) (A1)
Comments: This combination has been evaluated in the QUEST-1 • Patients with compensated cirrhosis with contra-
and QUEST-2 Phase III clinical trials in treatment-naïve patients indications to the use of ribavirin or with poor tolerance
[29,30]. The overall SVR rates were 80% (210/264) and 81% to ribavirin on treatment should receive the fixed-dose
(209/257), respectively. In a pooled analysis of both trials, combination of sofosbuvir and ledipasvir for 24 weeks
patients infected with subtype 1b achieved an SVR in 85% of cases without ribavirin (B1)
(228/267). Patients infected with subtype 1a achieved an SVR in
84% of cases (138/165) when no Q80K substitution was detect- • Treatment with the fixed-dose combination of sofosbuvir
able in the NS3 protease sequence at baseline. The SVR was only and ledipasvir with ribavirin can be prolonged to
58% (49/84) when a Q80K substitution was detectable at baseline 24 weeks in treatment-experienced patients with
by population sequencing. SVR was achieved with this regimen in compensated cirrhosis and negative predictors of
84% (317/378) of patients with an F0-F2 METAVIR score, 73% (60/ response, such as a platelet count <75 x 103/μl (B2)
12 Journal of Hepatology 2015 vol. xxx j xxx–xxx
Please cite this article in press as: EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol (2015), http://dx.doi.org/10.1016/
j.jhep.2015.03.025
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].
Genotype 1, IFN-containing Option 2
• Patients infected with HCV genotype 1 can be treated • Patients infected with HCV genotype 1 can be treated
with a combination of weekly PegIFN-α, daily weight- with the IFN-free fixed-dose combination of sofosbuvir
based ribavirin (1000 or 1200 mg in patients <75 kg or (400 mg) and ledipasvir (90 mg) in a single tablet
≥75 kg, respectively), and daily simeprevir (150 mg) administered once daily (A1)
(A1)
• Patients without cirrhosis, including treatment-naïve
• This combination is not recommended in patients and treatment-experienced patients, should be treated
infected with subtype 1a who have a detectable Q80K with this fixed-dose combination for 12 weeks without
substitution in the NS3 protease sequence at baseline, ribavirin (A1)
as assessed by population sequencing (direct sequence
analysis) (A1) • Treatment may be shortened to 8 weeks in treatment-
naïve patients without cirrhosis if their baseline HCV
• Simeprevir should be administered for 12 weeks in RNA level is below 6 million (6.8 Log) IU/ml. This should
combination with PegIFN-α and ribavirin. PegIFN-α be done with caution, especially in patients with F3
and ribavirin should then be administered alone for an fibrosis, pending demonstration of the accuracy of HCV
additional 12 weeks (total treatment duration 24 weeks) RNA level determination within this range of values
in treatment-naïve and prior relapser patients, including and real-life confirmation that 8 weeks of treatment are
cirrhotic patients, and for an additional 36 weeks (total sufficient to achieve high SVR rates (B1)
treatment duration 48 weeks) in prior partial and null
responders, including cirrhotic patients (B1) • Patients with compensated cirrhosis, including
treatment-naïve and treatment-experienced patients,
• HCV RNA levels should be monitored on treatment. should be treated with this fixed-dose combination for
Treatment should be stopped if HCV RNA level is ≥25 12 weeks with daily weight-based ribavirin (1000 or
IU/ml at treatment week 4, week 12 or week 24 (A2) 1200 mg in patients <75 kg or ≥75 kg, respectively) (A1)
Comments: This combination has been evaluated in the QUEST-1 • Patients with compensated cirrhosis with contra-
and QUEST-2 Phase III clinical trials in treatment-naïve patients indications to the use of ribavirin or with poor tolerance
[29,30]. The overall SVR rates were 80% (210/264) and 81% to ribavirin on treatment should receive the fixed-dose
(209/257), respectively. In a pooled analysis of both trials, combination of sofosbuvir and ledipasvir for 24 weeks
patients infected with subtype 1b achieved an SVR in 85% of cases without ribavirin (B1)
(228/267). Patients infected with subtype 1a achieved an SVR in
84% of cases (138/165) when no Q80K substitution was detect- • Treatment with the fixed-dose combination of sofosbuvir
able in the NS3 protease sequence at baseline. The SVR was only and ledipasvir with ribavirin can be prolonged to
58% (49/84) when a Q80K substitution was detectable at baseline 24 weeks in treatment-experienced patients with
by population sequencing. SVR was achieved with this regimen in compensated cirrhosis and negative predictors of
84% (317/378) of patients with an F0-F2 METAVIR score, 73% (60/ response, such as a platelet count <75 x 103/μl (B2)
12 Journal of Hepatology 2015 vol. xxx j xxx–xxx
Please cite this article in press as: EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol (2015), http://dx.doi.org/10.1016/
j.jhep.2015.03.025
