A regimen of boceprevir with pegylated
interferon and ribavirin achieved cure rates of between 40 and 68% in patients who
did not respond to a previous course of hepatitis C therapy, data presented to
the 47th International Liver Congress in Barcelona last week show.
The addition of boceprevir to standard
hepatitis C therapy (pegylated interferon/ribavirin) achieved a sustained
virological response 24-weeks post treatment (SVR24) in 40% of individuals with a prior
null response to treatment; in 56% of those who relapsed after an earlier
course of therapy; and in 68% of patients with a prior partial response.
Factors associated with the success of
treatment included baseline platelet count and viral load.
Boceprevir is a protease inhibitor which
works directly against hepatitis C. Its use with standard therapy – pegylated
interferon and ribavirin – has been shown to increase the chances of treatment-naive
individuals achieving a sustained virological response to therapy.
However the treatment of individuals who
have not responded successfully to standard therapy remains a challenge. There
are hopes that directly acting antiviral agents such as boceprevir will provide important
new therapeutic options.
Investigators therefore designed a study
involving 164 patients who had previously received an unsuccessful course of
pegylated interferon and ribavirin therapy. All had genotype-1 infection.
Approximately a third (31%) had a null
response to prior treatment (viral load decrease below 2 log10 copies
iu/ml after twelve weeks); 51% had a partial response (greater than 2 log10
copies iu/ml decrease at week twelve, but a detectable viral load at the end of
treatment); and 15% had relapsed (undetectable viral load at end of therapy but
The patients received four weeks of lead-in treatment with pegylated interferon and ribavirin, which was then combined with boceprevir (800mg three times a day), treatment lasting for a further 44 weeks. The study’s primary
endpoint was the proportion of patients who achieved a sustained virological
response (an undetectable viral load) 24 weeks after the completion of
Approximately two-thirds of the patients
were men, their average age was approximately 50 years, and 10% had liver cirrhosis.
A total of 138 patients were included in
the investigators’ final analysis. This included 53 patients who stopped
treatment early: 32 for treatment failure; eleven because of side-effects; and ten
for non-medical reasons.
Rates of treatment response differed
according to earlier outcomes. Some 68% of patients with an earlier partial
response achieved a sustained virological response. This compared to 56% of
individuals who had relapsed after therapy and 40% of individuals with a
previous null response.
Factors associated with a sustained
virological response 24-weeks post-treatment in a multiple stepwise logistic regression analysis included previous response to
treatment (null response: no vs yes; p = 0.0093); higher baseline platelet
count (>200,000) (p = 0.0017); male sex (p = 0.009) and a lower baseline viral load (below
800,000 copies iu/ml vs above 800,000 copies iu/ml; p = 0.073).
Almost all patients (96%) reported
side-effects and for 10% of patients these were serious. Treatment was
discontinued by 7% of patients because of adverse events and a third required
an adjustment in the dose of their medication. The most common side-effects
included anaemia (48%), fatigue (47%), nausea (30%) and headache (27%).
Strategies for the management of anaemia
included dose modification (26%), therapy with erythropoietin (40%) and
“Boceprevir with pegylated interferon/ribavirin is efficacious
in all three types of non-response: relapsers, partial responders and null
responders,” conclude the investigators. “The safety profile…was comparable to
that previously reported.”