AASLD: 派罗欣应考虑作为HBV的一线治疗

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AASLD: Consider Peginterferon as First-Line Therapy for Chronic Hepatitis B
Infection
By Mark L. Fuerst

BOSTON, MA -- November 2, 2004 -- Pegylated interferon should be considered
for first-line monotherapy in patients with chronic hepatitis B virus (HBV)
infection, according to the results of a large, randomized, multinational
study.


Previous data showed that peginterferon alfa-2a (Pegasys) yields
significantly higher response rates than lamivudine among hepatitis B
antigen (HbeAg)-positive patients with chronic hepatitis B. They also showed
that combining the two drugs does not improve response rates compared to
pegylated interferon alone.


George Lau, MD, assistant dean, University of Hong Kong, China, presented
findings from a comparative study here on October 31st at the 55th Annual
Meeting of the American Association for the Study of Liver Diseases.


The study evaluated the efficacy and safety of pegylated interferon with and
without lamivudine compared to lamivudine alone in 814 HBeAg-positive
patients with chronic hepatitis B. The patients, who ranged in age from 20
to 40 years and were predominantly Asian (85%-87%), were treated for 48
weeks and assessed after 24 weeks of treatment-free follow-up.


Treatment arms were divided as follows: 271 patients received pegylated
interferon 180 mcg once weekly plus placebo once daily; 271 patients
received pegylated interferon 180 mcg once weekly plus lamivudine 100 mg
daily; and 272 patients received lamivudine 100 mg daily.

Primary endpoints were HBeAg seroconversion (HBV DNA <100,000 copies/mL),
and secondary endpoints were HBeAg loss and normalization of alanine
transaminase (ALT) levels.

At week 72, one third of patients treated with pegylated interferon
monotherapy achieved seroconversion (P <.001) and one third achieved levels
of HBV DNA < 100,000 copies/mL (P =.012), statistically significant
differences in comparison to the lamivudine along group (19% and 22%,
respectively). Combination therapy with either drug achieved similar results
to pegylated interferon alone (27% and 34%, respectively). "Combining
pegylated interferon and lamivudine did not improve response rates over
pegylated interferon alone," Dr. Lau said.

"A curative therapy in one third of patients is a breakthrough," he added,
and noted that 16 patients in the pegylated interferon arm with or without
lamivudine achieved seroconversion compared to none in the lamivudine alone
arm.

"We never have seroconversion in Asians [who are treated with] with
nucleoside analogs," he said. "If patients seroconvert, their chance of
developing liver cirrhosis or liver cancer is greatly reduced."

The most marked seroconversion was among patients with ALT levels that were
more than 5 times the normal level, but 29% of patients who had 1 to 2 times
the normal liver enzyme level who were treated with pegylated interferon
achieved seroconversion. "atients with low ALT levels don't normally
respond to any form of therapy," Dr. Lau said.

Withdrawals from therapy were low (3% or less) for all three study arms. The
majority of adverse events were mild. More than half of those taking
lamivudine alone complained of at least one adverse event, he said. The
incidence of serious adverse events was low in all treatment groups (2%-6%).

"The addition of lamivudine did not significantly alter the pegylated
interferon safety profile," Dr. Lau said. Two patients taking lamivudine
alone had hepatic failure and one died. There were no treatment-related
deaths among the pegylated interferon patients.

"The better efficacy and very tolerable side effects profile together with
the fixed duration of therapy supports the use of pegylated interferon
monotherapy as first-line therapy in chronic hepatitis B, particularly for
young patients who doctors don't want to carry for 70 years with nucleoside
analogs," Dr. Lau said.

He said that he would reserve the use of lamivudine for selected patients
who are old, fragile, or immunosuppressed, or possibly as second-line
therapy for patients who do not respond to pegylated interferon.


[Presentation title: "eginterferon Alfa-2a (40KD) (Pegasys) Monotherapy and
in Combination With Lamivudine Is More Effective Than Lamivudine Monotherapy
in HbeAg-Positive Chronic Hepatitis B: Results From a Large, Multinational
Study." Abstract 20]

jackwen

有意思