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Information for Practicing Physicians
ROCHE Symposium Highlights
37th
Annual Meeting of the European Association for the Study of the Liver
MADRID,
SPAIN – APRIL 18-21, 2002
PEGINTERFERON
ALFA-2a plus ribavirin: 24 vs. 48 weeks and 800 vs. 1000/1200 mg ribavirin
A phase III study comparing the
efficacy of 24 weeks versus 48 weeks of combination therapy with peginterferon
alfa-2a, 180 mg weekly,
with differing ribavirin doses of 1000/1200 mg daily (standard) versus 800 mg
daily (low dose) was reported by Professor S. Hadziyannis in patients with
compensated liver disease due to chronic hepatitis C virus (HCV)
infection. Patients were stratified at
entry by genotype (1 vs. non-1) and viral titers (low vs. high as defined by
serum HCV RNA £ 2 or
>2 million copies/mL) as well as by geographic region. All patients were treatment naïve. The
genotype distribution was different for the 24-week versus 48-week regimens:
42% and 49% versus 62% and 69%, respectively, for the standard and low dose
ribavirin arms. Overall, patients were
predominantly male (63% to 68%) and in their early forties. Sustained virological response (SVR) was
defined as absence of serum HCV RNA 24 weeks following completion of therapy.
For genotype 1 patients, the SVR
was 51% for patients treated with 48 weeks of peginterferon alfa-2a 180 mg weekly
plus ribavirin 1000/1200 mg/d compared to 40% with 48 weeks of peginterferon
and ribavirin 800 mg/d. Therapy for 24 weeks yielded an SVR of 41% and 29%,
respectively, for the standard-dose and low-dose ribavirin regimens, indicating
that genotype 1 patients require longer duration therapy and the higher dose of
ribavirin for maximal efficacy. For patients with genotype 1 and low viral
load, the SVR was 61% with 48 weeks of ribavirin 1000/1200 mg daily; for
patients with genotype 1 and high viral titers, the SVR was 46%. For non-genotype 1 patients, the SVR was 73%
to 78% across all treatment arms. The
SVR for cirrhotic patients was 50% with standard-dose ribavirin over 48 weeks
compared to 61% in non-cirrhotics.
Treatment withdrawals due to adverse events were 3.5% to 3.7% in the
24-week regimens and 12.4% to 14.2% in the 48-week regimens.
Important conclusions from this
study are that: 1) peginterferon alfa-2a plus ribavirin yielded a SVR of 61%
overall; 2) the SVR in non-cirrhotics was 65% versus 50% in cirrhotics; 3) in
genotype 1 patients, 48 weeks of peginterferon plus ribavirin at a dose of
1000/1200 mg/d achieved a SVR of 51% (the SVR in patients with a high viral
load was 46% vs. 61% in those with a low viral load); 4) in non-genotype 1
patients, a shorter duration of therapy (24 week) and a lower dose of ribavirin
(800 mg/d) was adequate therapy (73% to 78% SVR), with no increased efficacy
with longer therapy or higher doses of ribavirin.
predictability of sustained virological
response
Dr. Donald Jensen from Rush
Presbyterian in Chicago addressed the issue of predictability of SVR in
patients receiving peginterferon alfa-2a and ribavirin therapy. In a study of 453 patients receiving this
combination for 48 weeks, 86% had had an early virological response (EVR)
defined as serum HCV RNA negativity or at least a 2-log drop in HCV RNA levels
after 12 weeks of therapy. Patients who
took 80% or more of their medication doses and completed at least 38 weeks of
therapy, which was defined as “full dose”, and who also had an EVR ultimately
had a SVR of 75%. In genotype 1
patients, the group with an EVR and meeting the full dose criteria had a SVR of
67%. For patients with genotypes 2 or
3, patients who had an EVR and satisfied the full dose criteria had a SVR of
88%.
These data suggest that the EVR
after 12 weeks of therapy is highly predictive of a SVR and is more useful than
baseline parameters in determining response rates. Absence of EVR was useful in predicting non-response, with a
negative predictive value of 97%. Use
of EVR will allow individualization of treatment regimens and provide a basis
for advocating adherence to therapy.
Problem patient
groupS
Professor Graham Cooksley from
Brisbane reviewed studies reported to date on difficult-to-treat populations
with HCV infection. End-of-treatment
responses with peginterferon alfa-2a and ribavirin in patients who were
nonresponders and relapsers to prior standard interferon alfa-2b and ribavirin
were 25% and 61%, respectively, suggesting that retreatment will result in a
reasonable SVR even in prior nonresponders. In patients coinfected with human
immunodeficiency virus (HIV) and HCV, the virological response was 44% at week
24 with peginterferon alfa-2a compared to only 15% with a high-dose induction
regimen with standard interferon plus ribavirin. In liver transplant recipients with recurrent chronic hepatitis
C, an end-of-treatment response of 36% was observed with peginterferon alfa-2a
monotherapy. Finally, a preliminary report
demonstrated efficacy of peginterferon alfa-2a in patients with HBeAg-positive
chronic hepatitis B.
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