Telaprevir (brand name
Incivo) is a new medication used to
treat hepatitis C. It was approved in Europe in September 2011 for treatment of
adults with genotype 1 chronic hepatitis C in combination with pegylated
interferon and ribavirin.
Overall, telaprevir triple
therapy cures about 75% of people who take it, but it works better for some
groups than others. Successful treatment reduces the risk of long-term complications
of hepatitis C such as liver cancer or needing a liver transplant.
Telaprevir is no longer available in the United States. Telaprevir
is still licensed in the European Union but is no longer recommended as an
appropriate treatment for hepatitis C by the European Association for the Study
of the Liver, owing to a higher rate of side-effects and a lower cure rate when
compared to newer interferon-free treatments licensed since 2014.
How does telaprevir work?
Telaprevir is one of
the new direct-acting antiviral drugs that target different steps of the
hepatitis C virus (HCV) lifecycle. It is an HCV protease inhibitor, meaning it
blocks the protease enzyme which the virus must use to reproduce. Telaprevir
must be combined with two older drugs: pegylated interferon, which stimulates
the body's own immune response against the virus, and ribavirin, which improves
the effectiveness of interferon.
Who can use telaprevir?
indicated for use by adults with chronic hepatitis C, meaning infection lasting
more than six months. It is approved for people with HCV genotype 1, which is
the most common type in Europe and considered the hardest to treat. It is not
approved and should not be used to treat other HCV genotypes.
Telaprevir can be used
by people being treated for hepatitis C for the first time (known as
'treatment-naive') and for retreatment of people who were not cured with
previous interferon-based therapy.
Telaprevir has also been
tested in people with HIV and HCV co-infection. Response rates and side-effects are
similar to those of HIV-negative people, but telaprevir can interact with some
HIV drugs. People with HIV and HCV co-infection who want to take telaprevir should
do so under the care of a doctor who has experience treating both infections.
Telaprevir can be used
by people with all stages of compensated liver disease including cirrhosis.
However, it works better for people with less advanced liver damage. Also,
people with cirrhosis who take telaprevir may experience more serious
side-effects. Telaprevir triple therapy can be dangerous and therefore should
not be used by people with decompensated liver disease, or liver failure.
How is telaprevir taken?
Telaprevir is a pill
that may be taken as either three tablets twice daily or two tablets three
times daily. It should be taken with food. Telaprevir must be used with weekly
pegylated interferon injections and twice-daily ribavirin pills. Telaprevir is
not effective if taken alone, and this can lead to drug resistance.
All three drugs are
taken together for 12 weeks. Then interferon and ribavirin alone are taken for
an additional 12 or 36 weeks, depending on early response, previous treatment
history and extent of liver damage. This is known as 'response-guided therapy'.
Many people can be successfully treated in a total of 24 weeks - half the duration of interferon/ribavirin
How effective is telaprevir?
works better for some people than for others. Several factors predict how well
someone will respond. Telaprevir is only approved for genotype 1 hepatitis C.
It is not proven effective against genotypes 2, 3 or 4. Different direct-acting
antivirals work better against these other genotypes.
One of the most
important factors is previous treatment history. People who are new to
treatment, and those who relapsed after finishing previous treatment, have the
best chance of being cured with telaprevir. Telaprevir triple therapy does not
work as well for people who had only a partial response or no response to prior
- Sustained responder: a person who was successfully treated and
cured of hepatitis C.
- Relapser: a person who reached undetectable HCV viral load with previous
interferon-based therapy, but relapsed, or saw the virus return, after
- Partial responder: a person who had some decrease in HCV viral
load with previous treatment, but did not reach an undetectable level.
- Null responder: a person who had little or no decrease in HCV
viral load with previous treatment.
People with less
advanced liver damage respond better to treatment. People with cirrhosis are
less likely to be cured with telaprevir triple therapy and they may have more
problems with drug side-effects.
Telaprevir treatment response
People who experience
a rapid drop in HCV viral load soon after starting treatment are more likely to
be cured. Undetectable viral load at week 4 of treatment (known as 'rapid
virological response' or RVR) and at the end of 12 weeks of telaprevir triple
therapy is a good predictor of who will be cured. This will make some patients
eligible for shorter treatment. But people who do not respond well after the
first 4 or 12 weeks should stop treatment, as it is unlikely to work if
People with sustained
virological response, who still have undetectable viral load at 12 or 24 weeks
after finishing treatment (known as 'SVR12' or 'SVR24'), are considered cured.
A clinical study called
ADVANCE tested 12 weeks of telaprevir triple therapy followed by pegylated
interferon/ribavirin alone for an additional 12 or 36 weeks. 75% of previously
untreated people who took triple therapy were cured, compared with 44% of those
who took only pegylated interferon and ribavirin.
Another study called REALIZE
tested telaprevir triple therapy for 12 weeks followed by pegylated
interferon/ribavirin for 36 weeks for previously treated people. Among prior
relapsers, 83% of people who took telaprevir were cured, compared with 24% who
took only pegylated interferon and ribavirin. But telaprevir sustained response
rates were lower for previous partial responders (59%) and null responders (29%).
Telaprevir has also
been tested in people with HIV and HCV co-infection, showing response rates and
side-effects similar to those of people with hepatitis C alone. In one study, 74%
of previously untreated patients with co-infection who took telaprevir triple therapy were
cured, compared with 45% who took only pegylated interferon and ribavirin.
effectiveness in 'real world' use is somewhat lower than cure rates seen in
clinical trials, in part because patients may be sicker or have other
conditions that can make treatment more difficult.
therapy has been tested in people with advanced liver disease, including people
who are awaiting or have received liver transplants. Sustained response rates
are higher than those of pegylated interferon/ribavirin alone, but people with
advanced liver disease often have trouble tolerating treatment side-effects.
What are the side-effects of telaprevir?
Telaprevir can cause
some side-effects of its own, but many symptoms in people taking triple therapy
are due to pegylated interferon or ribavirin. The most common side-effects of
telaprevir are anaemia (low haemoglobin level), nausea, diarrhoea, skin rash,
itching and anal discomfort. Skin rash is usually mild to moderate, but 5% may develop
a severe rash.
interferon include headache, fatigue, muscle and joint aches and depression.
Ribavirin also causes anaemia, which can be worse when combined with
telaprevir. Ribavirin can cause birth defects and should not be used by
pregnant women or their male partners.
Does telaprevir interact with other drugs?
interact with other drugs that are processed by the same enzymes in the liver.
These include some antiretroviral drugs for HIV, TB medications, heart disease
drugs and psychiatric medications. Sometimes drug doses can be adjusted to
overcome these interactions, but some medications should not be used together
with telaprevir. Information about specific drug interactions is available
online at www.hep-druginteractions.org.
How can I get telaprevir?
available by prescription in European Union countries to treat genotype 1
hepatitis C. Ask your GP or liver specialist if telaprevir combination therapy
may be a good option.
When to start
treatment will depend on a number of factors, including severity of liver damage
(as determined by FibroScan or a
liver biopsy). People with mild liver disease may be able to wait, and new more
effective and better-tolerated hepatitis C medications that can be used without
interferon are coming soon. However, the decision to wait must take into
account how fast your liver disease might progress - which is hard to predict - and how soon new treatments
will be approved in your country.