Page 21 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 21
Clinical Practice Guidelines Monitoring treatment safety
Recommendations PegIFN-a-containing regimens .
Flu-like symptoms are often present after PegIFN-a injections.
• A real-time PCR-based assay with a lower limit of
detection of ≤15 IU/ml should be used to monitor HCV They are easily controlled by paracetamol and tend to attenuate
RNA levels during and after therapy (A1) after 4–6 weeks of therapy. At each visit, the patients should be
assessed for clinical side effects, such as severe fatigue, depres-
• In patients treated with the triple combination of sion, irritability, sleeping disorders, skin reactions and dyspnoea.
PegIFN-α, ribavirin and sofosbuvir for 12 weeks, HCV Thyroxin and thyroid stimulating hormone (TSH) levels should be
RNA should be measured at baseline and at weeks 4, measured every 12 weeks while on therapy [60].
12 (end of treatment), and 12 or 24 weeks after the end
of therapy (A2) Haematological side effects of PegIFN-a and ribavirin include
• In patients treated with the triple combination of neutropenia, anaemia, thrombocytopenia and lymphopenia.
PegIFN-α, ribavirin and simeprevir (12 weeks plus 12 or These parameters should be assessed at weeks 1, 2, and 4 of ther-
36 weeks of PegIFN-α and ribavirin alone), HCV RNA apy and at 4 to 8 week intervals thereafter.
should be measured at baseline, week 4, week 12,
week 24 (end of treatment in treatment-naïve patients Ribavirin-containing regimens
and prior relapsers), week 48 (end of treatment in prior Mild anaemia can occur in IFN-free regimens containing rib-
partial and null responders), and 12 or 24 weeks after
the end of therapy (A2) avirin; indeed, haemoglobin decreases have been greater and
more common when DAAs were combined with ribavirin than
• In patients treated with an IFN-free regimen, HCV RNA in regimens without ribavirin.
should be measured at baseline, week 2 (assessment
of adherence), week 4, week 12 or 24 (end of treatment Significant teratogenic and/or embryocidal effects have been
in patients treated 12 or 24 weeks, respectively), and 12 demonstrated in all animal species exposed to ribavirin.
or 24 weeks after the end of therapy (A2) Women of childbearing potential and/or their male partners
must use an effective form of contraception during treatment
and for a period of 6 months after the treatment has concluded.
Recommendations
Stopping (futility) rules • Women of childbearing potential and/or their male
partners must use an effective form of contraception
Futility rules have been defined only with the triple combination during ribavirin-containing treatment and for a period of
6 months after the treatment has concluded (A1)
of PegIFN-a, ribavirin and simeprevir.
DAA-containing regimens
Recommendations New DAA regimens are generally well tolerated. Frequencies of
high grade or serious adverse events leading to discontinuation
• With the triple combination of PegIFN-α, ribavirin and of IFN-free regimens are low. However, data in patients with
simeprevir, treatment should be stopped if HCV RNA decompensated cirrhosis or in liver transplant recipients are
level is ≥25 IU/ml at treatment week 4, week 12 or week scarce. The efficacy and toxicity of concurrent drugs given for
24 (A2) comorbidities and
potential drug-drug interactions should be monitored during
• An immediate switch to another IFN-containing DAA- treatment.
containing or to an IFN-free regimen without a protease
inhibitor should be considered (B1) Simeprevir. Patients receiving simeprevir may experience
mild to moderate rashes and photosensitivity; sun protection
• No futility rules have been defined for other treatment measures and limiting sun exposure is necessary. Indirect hyper-
regimens (A1) bilirubinaemia may occur, but the increment in bilirubin concen-
trations is less in patients not receiving ribavirin. Patients of East
20
Recommendations PegIFN-a-containing regimens .
Flu-like symptoms are often present after PegIFN-a injections.
• A real-time PCR-based assay with a lower limit of
detection of ≤15 IU/ml should be used to monitor HCV They are easily controlled by paracetamol and tend to attenuate
RNA levels during and after therapy (A1) after 4–6 weeks of therapy. At each visit, the patients should be
assessed for clinical side effects, such as severe fatigue, depres-
• In patients treated with the triple combination of sion, irritability, sleeping disorders, skin reactions and dyspnoea.
PegIFN-α, ribavirin and sofosbuvir for 12 weeks, HCV Thyroxin and thyroid stimulating hormone (TSH) levels should be
RNA should be measured at baseline and at weeks 4, measured every 12 weeks while on therapy [60].
12 (end of treatment), and 12 or 24 weeks after the end
of therapy (A2) Haematological side effects of PegIFN-a and ribavirin include
• In patients treated with the triple combination of neutropenia, anaemia, thrombocytopenia and lymphopenia.
PegIFN-α, ribavirin and simeprevir (12 weeks plus 12 or These parameters should be assessed at weeks 1, 2, and 4 of ther-
36 weeks of PegIFN-α and ribavirin alone), HCV RNA apy and at 4 to 8 week intervals thereafter.
should be measured at baseline, week 4, week 12,
week 24 (end of treatment in treatment-naïve patients Ribavirin-containing regimens
and prior relapsers), week 48 (end of treatment in prior Mild anaemia can occur in IFN-free regimens containing rib-
partial and null responders), and 12 or 24 weeks after
the end of therapy (A2) avirin; indeed, haemoglobin decreases have been greater and
more common when DAAs were combined with ribavirin than
• In patients treated with an IFN-free regimen, HCV RNA in regimens without ribavirin.
should be measured at baseline, week 2 (assessment
of adherence), week 4, week 12 or 24 (end of treatment Significant teratogenic and/or embryocidal effects have been
in patients treated 12 or 24 weeks, respectively), and 12 demonstrated in all animal species exposed to ribavirin.
or 24 weeks after the end of therapy (A2) Women of childbearing potential and/or their male partners
must use an effective form of contraception during treatment
and for a period of 6 months after the treatment has concluded.
Recommendations
Stopping (futility) rules • Women of childbearing potential and/or their male
partners must use an effective form of contraception
Futility rules have been defined only with the triple combination during ribavirin-containing treatment and for a period of
6 months after the treatment has concluded (A1)
of PegIFN-a, ribavirin and simeprevir.
DAA-containing regimens
Recommendations New DAA regimens are generally well tolerated. Frequencies of
high grade or serious adverse events leading to discontinuation
• With the triple combination of PegIFN-α, ribavirin and of IFN-free regimens are low. However, data in patients with
simeprevir, treatment should be stopped if HCV RNA decompensated cirrhosis or in liver transplant recipients are
level is ≥25 IU/ml at treatment week 4, week 12 or week scarce. The efficacy and toxicity of concurrent drugs given for
24 (A2) comorbidities and
potential drug-drug interactions should be monitored during
• An immediate switch to another IFN-containing DAA- treatment.
containing or to an IFN-free regimen without a protease
inhibitor should be considered (B1) Simeprevir. Patients receiving simeprevir may experience
mild to moderate rashes and photosensitivity; sun protection
• No futility rules have been defined for other treatment measures and limiting sun exposure is necessary. Indirect hyper-
regimens (A1) bilirubinaemia may occur, but the increment in bilirubin concen-
trations is less in patients not receiving ribavirin. Patients of East
20
