Treatment adherence in patients treated with telaprevir for a chronic hepatitis C genotype 1 infection: an observational study

Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis. HCV is
endemic in most parts of the world, and is estimated that at least 170 million
people are or have been infected with HCV worldwide. Approximately 20%-30% of
patients with chronic HCV infection will develop cirrhosis. Death related to
the complications of cirrhosis occurs at an incidence of approximately 4% per
year, whereas hepatocellular carcinoma (HCC) is detected in this population at
a rate of 1-5% per year. HCV related end-stage liver disease is now the main
indication for liver transplantation in the USA and Western Europe.
Hepatits C genotype 1 is responsible for most HCV infections in Europe, Asia
and the United States. Treatment with pegylated-interferon-alfa and ribavirin
(Peg/RBV) is only effective in 40%-50% of patients and associated with
significant side effects. In several recent clinical trials, telaprevir, an
orally bioavailable inhibitor of the nonstructural 3/4A HCV protease,
substantially enhance rates of sustained virologic response when combined with
peginterferon plus ribavirin in patients. In treatment-naïve patients rate of
treatment success doubled in patients treated with pegylated-interferon-alfa,
ribavirin and telaprevir to 72%. In 65% of patients treatment duration can be
shortened to 24 weeks instead of 48 weeks. The changes of treatment success
decrease to 63% in patients with significant fibrosis and/or cirrhosis.
Adherence to Peg/RBV is essential since dose reductions and non-compliance are
associated with a reduction of sustained viral response rates. It is likely
that the addition of telaprevir to the current standard of care will be
challenging for patients due to the need to take telaprevir with a fatty meal
to achieve adequate plasma levels of telaprevir. It was previously shown that
only about half of the patients who were prescribed a regimen with three times
daily dosing together with dietary instructions for the treatment of HIV-1
infection were able to be fully adherent to such regimens.
Depression is a common side effect of treatment with Peg/RBV. Depression is one
of the most important risk factors for having low levels of medication
adherence. We therefore anticipate that depression could have a negative
influence on the levels of adherence of patients who are treated with
telaprevir and Peg/RBV.
The proposed study will establish to what extent patients who are receiving
telaprevir and Peg/RBV in routine clinical practice are able to adhere to their
treatment regimen. If the proposed study would yield low levels of adherence,
this would suggest that additional adherence monitoring and support would be
required in routine clinical practice.

Primary objective

To establish the mean level of adherence to telaprevir in chronic hepatitis C
patients during treatment with telaprevir, pegylated-interferon-alfa and
ribavirin.

Secondary objectives
• To establish the mean level of adherence to ribavirin in chronic hepatitis C
patients during treatment with pegylated-interferon-alfa and ribavirin
following 12 weeks of treatment with telaprevir, pegylated-interferon-alpha and
ribavirin.
• To explore the effects of different levels of adherence to telaprevir on the
likelihood of achieving rapid virological response (RVR) and sustained
virologic response.
• To explore the effects of different levels of adherence to ribavirin on the
likelihood of achieving rapid virological response (RVR) and sustained
virologic response.
• To assess changes in adherence to telaprevir and ribavirin over time.
• To assess telaprevir and ribavirin trough levels
• To explore the effects of telaprevir and ribavirin trough levels on the
likelihood of achieving rapid virological response (RVR) and sustained
virologic response.
• To investigate the association between adherence to telaprevir and ribavirin
and the presence of depression and anxiety symptoms

open label single arm observational study

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