Treatment
Extension to 72 Weeks of PegIntron plus Weight-based Ribavirin Improves SVR Rates
in Difficult-to-Treat Slow Responders with Genotype 1
The
results of several studies among chronic HCV patients with genotype
1 suggest that the duration of therapy with interferon and ribavirin is an
important cofactor for achieving a sustained
virologic response (SVR).
In
the current study, conducted by Dr. Brian Pearlman and colleagues at the Center
for Hepatitis C and the Atlanta Medical Center in Atlanta, GA, the investigators
sought to determine if slow virologic responders would benefit from an extension
of the duration of therapy with peginterferon
alfa-2b (PegIntron) plus weight-based ribavirin.
In
a study published earlier this year, improvement in SVR rates and relapse rates
was shown among patients in whom treatment was extended from 48 weeks to 72 weeks
(Gastroenterology 130:1357, 2006). However, previous studies utilized doses
of ribavirin (800 mg daily) that appear to be suboptimal for genotype 1 infection,
according to the authors of the present study. Furthermore, the authors note,
it is unclear if extending therapy could also benefit more difficult-to-treat
patients, such as African Americans.
The
researchers enrolled 86 treatment-naïve, HCV patients with elevated ALT and
genotype 1 in this single center Atlanta study. Patients received 1.5 mcg/kg/week
of PegIntron and 800-1,400 mg/day of ribavirin, dosed according to weight.
All
the study participants were slow responders to therapy (defined as at least a
2-log drop in HCV RNA from baseline value, but having detectable HCV RNA at 12
weeks (Roche TaqMan PCR, detection limit 10 IU/ml). Patients were randomized 1:1
to continue treatment to complete a total of 48 or 72 weeks.
HCV
RNA was rechecked at week 24, at the end of treatment and at the end of a 24 week
treatment-free follow-up interval.
Results
Demographic, biochemical and virologic baseline characteristics were not statistically
different between groups.
Overall, 48% of patients were African American [unusually high for a US study-Ed];
79% had high viral load; 24% had F3/4 fibrosis, and 31% had a body mass index
of 30 or above.
All patients had undetectable HCV RNA at 24 weeks of therapy.
Dose reductions and treatment discontinuations for adverse events or laboratory
abnormalities were similar between groups.
The end-of-treatment response rates were significantly higher in the 72-week group
compared to those in the 48-week group (54% versus 33%, respectively; p=0.04).
Relapse
rates were 28% in the 72 week treatment group compared to 46% in the 48 week treatment
group (p=ns).
Overall, the rate of SVR was superior in patients treated for 72 weeks versus
48 weeks (39% versus 18%, respectively; p=0.03).
Based
on these findings, the authors conclude, "Extending the treatment duration
from 48 weeks to 72 weeks in genotype-1 infected patients with slow virologic
response to peginterferon alfa-2b and weight-based ribavirin significantly improves
SVR rates."
"Treatment
extension does not seem to increase the rate of dose reduction or therapy discontinuation."
"Results
need to be confirmed in larger studies."
Center
for Hepatitis C, Atlanta, GA, USA, and the Atlanta Medical Center, Atlanta, GA,
USA.
11/03/06
Reference B
Pearlman, C Ehleben, and S Saifee. Improved Virologic Response Rates with Treatment
Extension to 72 Weeks of Peginterferon Alfa-2B plus Weight-based Ribavirin in
a Difficult-to-Treat Population of Genotype 1-infected Slow Responders. 57th AASLD.
October 27-31, 2006. Boston, MA. Abstract 343.
Demographic, biochemical and virologic baseline characteristics were not statistically
different between groups. 
