RGT is a dynamic algorithm that involves individualized
treatment based on the on-treatment virologic response.
Basically, the more rapidly HCV RNA becomes negative during
treatment, the higher the rate of SVR.
Several types of virological responses may occur, categorized
according to their timing during treatment (Di Bisceglie 2007,
McHutchinson 2009):
Antiviral Therapy: The Basics | 25
– rapid virological response (RVR): undetectable HCV RNA
at week 4 (measured by real-time PCR assay with lower limit
of detection <15 IU/mL)
– early virological response (EVR), assessed at week 12
– complete EVR (cEVR): undetectable HCV RNA at week 12
– partial EVR (pEVR): decrease of HCV RNA by >2 log10 (100
fold) from baseline values at week 12
– end-of-treatment virological response (EoTR):
undetectable HCV RNA at the end of therapy (week 24 for
genotypes 2/3 or week 48 for genotypes 1/4)
– sustained virologic response (SVR): undetectable HCV
RNA 6 months after completing therapy
The standard recommended duration of treatment (Table 1.2) is
48 weeks for HCV genotypes 1/4 (with SVR rates of about 50%
and 65%, respectively) and 24 week for genotypes 2/3 (with
SVR rates of more than 75%). There is so far insufficient
experience to provide recommendations for HCV genotypes 5/6.
High weight-based dose RBV (15 mg/kg body) is recommended
for patients with baseline factors suggesting low responsiveness
(IR, metabolic syndrome, severe fibrosis or cirrhosis, older age).
The most important marker of treatment success is SVR. An
EoTR does not accurately predict a SVR, but is necessary for it to
occur. A RVR is the best predictor of SVR, if patients fulfill the
complete duration of treatment. The absence of an EVR is highly
predictive of treatment failure.
Treatment should be stopped at
– week 12 if the HCV RNA decrease is less than 2 log10 IU/ml,
compared with the baseline value (the SVR rate in these
patients is less than 2%)
– week 24 in patients with detectable HCV RNA (>50 IU/ml),
due to a minimal chance of SVR (1–3%)
26 | Hepatitis C Treatment
Table 1.2 – First-line treatment recommendations for antiviral
therapy in Hepatitis C*
HCV
Genotypes
PegIFN alfa-2a
once per week
PegIFN alfa-2b
once per week
RBV
once per day
Planned
duration†
1 and 4 180 μg
Flat dose
1.5 μg/kg
weight-based
dose
15 mg/kg weightbased
dose
48 weeks
800 mg daily
flat dose, if BMI<25
2 and 3 180 μg
Flat dose
1.5 μg/kg
weight-based
dose 15 mg/kg weightbased
dose, if
BMI>25
24 weeks
*According to data from EASLD 2011
†Treatment duration should be tailored to the on-treatment virological response
at weeks 4 and 12, and eventually, week 24.
For RGT, the following recommendations can be made
(Tsubota 2011):
– Treatment duration can be reduced to 12 weeks for
genotypes 2/3 infected patients who obtain an RVR with
PegIFN and weight-based RBV dosing. This does not
compromise the likelihood of achieving an SVR, but reduce
the AEs and the associated costs.
– Treatment duration can be reduced to 24 weeks for
genotype 1 infected patients with low baseline
(pretreatment) VL who attain a RVR.
– Treatment may be extended to 72 weeks for genotype 1
infected patients who show a slow virological response (with
partial EVR and HCV RNA negative by week 24). However,
for those who do not attain an EVR, the chance of treatment
success is very low (Thomson 2008).
In the clinical trials of the new direct-acting antivirals, a new
marker has been implemented, namely extended RVR (Sherman
2010). Extended RVR (eRVR) is defined as undetectable HCV
RNA at week 4 of therapy, maintained through a later time point
(in some cases over a period of 12 weeks, in others over 24
weeks). eRVR is a good predictor of the ability to shorten triple
therapy with protease inhibitors. Patients with G1 HCV, who
Antiviral Therapy: The Basics | 27
obtain an eRVR under triple therapy containing a protease
inhibitor, are eligible for RGT and a shortened duration of
treatment (24 weeks). Failure to achieve an eRVR cannot be used
as a stopping rule; continuation of therapy leads to SVR in a
considerable number of patients.
treatment based on the on-treatment virologic response.
Basically, the more rapidly HCV RNA becomes negative during
treatment, the higher the rate of SVR.
Several types of virological responses may occur, categorized
according to their timing during treatment (Di Bisceglie 2007,
McHutchinson 2009):
Antiviral Therapy: The Basics | 25
– rapid virological response (RVR): undetectable HCV RNA
at week 4 (measured by real-time PCR assay with lower limit
of detection <15 IU/mL)
– early virological response (EVR), assessed at week 12
– complete EVR (cEVR): undetectable HCV RNA at week 12
– partial EVR (pEVR): decrease of HCV RNA by >2 log10 (100
fold) from baseline values at week 12
– end-of-treatment virological response (EoTR):
undetectable HCV RNA at the end of therapy (week 24 for
genotypes 2/3 or week 48 for genotypes 1/4)
– sustained virologic response (SVR): undetectable HCV
RNA 6 months after completing therapy
The standard recommended duration of treatment (Table 1.2) is
48 weeks for HCV genotypes 1/4 (with SVR rates of about 50%
and 65%, respectively) and 24 week for genotypes 2/3 (with
SVR rates of more than 75%). There is so far insufficient
experience to provide recommendations for HCV genotypes 5/6.
High weight-based dose RBV (15 mg/kg body) is recommended
for patients with baseline factors suggesting low responsiveness
(IR, metabolic syndrome, severe fibrosis or cirrhosis, older age).
The most important marker of treatment success is SVR. An
EoTR does not accurately predict a SVR, but is necessary for it to
occur. A RVR is the best predictor of SVR, if patients fulfill the
complete duration of treatment. The absence of an EVR is highly
predictive of treatment failure.
Treatment should be stopped at
– week 12 if the HCV RNA decrease is less than 2 log10 IU/ml,
compared with the baseline value (the SVR rate in these
patients is less than 2%)
– week 24 in patients with detectable HCV RNA (>50 IU/ml),
due to a minimal chance of SVR (1–3%)
26 | Hepatitis C Treatment
Table 1.2 – First-line treatment recommendations for antiviral
therapy in Hepatitis C*
HCV
Genotypes
PegIFN alfa-2a
once per week
PegIFN alfa-2b
once per week
RBV
once per day
Planned
duration†
1 and 4 180 μg
Flat dose
1.5 μg/kg
weight-based
dose
15 mg/kg weightbased
dose
48 weeks
800 mg daily
flat dose, if BMI<25
2 and 3 180 μg
Flat dose
1.5 μg/kg
weight-based
dose 15 mg/kg weightbased
dose, if
BMI>25
24 weeks
*According to data from EASLD 2011
†Treatment duration should be tailored to the on-treatment virological response
at weeks 4 and 12, and eventually, week 24.
For RGT, the following recommendations can be made
(Tsubota 2011):
– Treatment duration can be reduced to 12 weeks for
genotypes 2/3 infected patients who obtain an RVR with
PegIFN and weight-based RBV dosing. This does not
compromise the likelihood of achieving an SVR, but reduce
the AEs and the associated costs.
– Treatment duration can be reduced to 24 weeks for
genotype 1 infected patients with low baseline
(pretreatment) VL who attain a RVR.
– Treatment may be extended to 72 weeks for genotype 1
infected patients who show a slow virological response (with
partial EVR and HCV RNA negative by week 24). However,
for those who do not attain an EVR, the chance of treatment
success is very low (Thomson 2008).
In the clinical trials of the new direct-acting antivirals, a new
marker has been implemented, namely extended RVR (Sherman
2010). Extended RVR (eRVR) is defined as undetectable HCV
RNA at week 4 of therapy, maintained through a later time point
(in some cases over a period of 12 weeks, in others over 24
weeks). eRVR is a good predictor of the ability to shorten triple
therapy with protease inhibitors. Patients with G1 HCV, who
Antiviral Therapy: The Basics | 27
obtain an eRVR under triple therapy containing a protease
inhibitor, are eligible for RGT and a shortened duration of
treatment (24 weeks). Failure to achieve an eRVR cannot be used
as a stopping rule; continuation of therapy leads to SVR in a
considerable number of patients.
No comments:
Post a Comment