A third study, however, did not see a
benefit of pegylated interferon following a short course of nucleoside/nucleotide
Presented by Wei-Wen Su from Changhua Christian Hospital,
the NEED trial included 280 people with HBeAg-positive chronic hepatitis B in Taiwan. About
70% were men and the mean age was 38 years. About 60% were treatment-naive, 20%
had previously used interferon and 30% had previously used
Participants in this double-blind trial
were randomly assigned (1:1:1) to receive entecavir, adefovir (Hepsera) or placebo for six weeks.
Starting at week 4, they added pegylated interferon and stayed on triple
therapy for two weeks, then continued on interferon alone through week 52.
At 52 weeks, the rate of HBeAg
seroconversion was numerically higher in the pegylated interferon monotherapy
arm (27%) than in the groups that received short-term entecavir or adefovir
(22% and 21%, respectively), but the differences were not statistically significant.
After a further 24 weeks of off-treatment
follow-up, HBeAg seroconversion rates were 36%, 28% and 23% – again not
significant differences (though the pegylated interferon vs adefovir comparison
came close to significance).
HBV DNA levels, however, declined significantly more
in the entecavir and adefovir arms than in the pegylated interferon monotherapy
arm; entecavir also reduced viral load significantly more than adefovir.
Treatment was again described as generally well-tolerated.
Approximately 10% of participants experienced serious adverse events, but only
seven people withdrew early due to adverse events. The most common side-effects
were hair loss, headache, fever and muscle aches.
"This kind of sequential combination
strategy does not increase the HBeAg seroconversion rate compared to pegylated
interferon alfa-2a monotherapy at the end of treatment or at 24 weeks,"
the investigators concluded. "A strategy of initial combination with
[nucleoside/nucleotide analogues] for a longer treatment duration to achieve a
lower HBV DNA level before starting pegylated interferon requires further
Su explained that the researchers
hypothesized that by not fully suppressing HBV viral load before starting
pegylated interferon, the residual virus would give interferon-stimulated
immune responses something to work on, but this strategy proved ineffective.
Reporters at the press conference
questioned the claim that pegylated interferon is 'well tolerated', given the
well-known difficult side-effects
seen among people taking the treatment for hepatitis C.
"If a disease is more difficult, the side-effect
threshold goes up," Yurdaydin explained. "In hepatitis C we now have
the luxury of getting rid of pegylated interferon. If we had the luxury in
hepatitis B, we would do it too."
He noted that the cost of ongoing
nucleoside/nucleotide analogue therapy is often prohibitive, so any way to
shorten treatment duration is important. "Together, these ground-breaking
data will go a long way to influencing future chronic hepatitis B treatment
guidelines," he predicted.