Assessment
of Viral Kinetics Helps Predict Response to Treatment with Pegylated Interferon
Alfa plus Ribavirin in Chronic Hepatitis C Patients Clinicians
are increasingly utilizing assessment of viral kinetics in response to pegylated
interferon alfa plus ribavirin to help predict treatment response among patients
with chronic hepatitis C, according to study results presented at the 58th Annual
Meeting of the American Association for the Study of Liver Diseases (AASLD 2007)
in Boston (November 2-6, 2007). HCV
RNA levels decrease rapidly after initiation of treatment with pegylated
interferon plus ribavirin. To determine the value of assessing early viral
kinetics during therapy, researchers conducted a review of articles and abstracts
looking at positive and negative predictive values (PPV; NPV) of rapid virological
response (RVR) and early virological response (EVR) for sustained virological
response (SVR) among patients receiving pegylated interferon alfa-2b (PegIntron).
PPVs and NPVs
were calculated if they were not reported but RVR and/or EVR rates and SVR rates
were available. RVR was defined as undetectable HCV RNA at week 4 of treatment
(lower limit of detection < 50 IU/mL in most studies). EVR was defined as undetectable
HCV RNA or at least a 2 log10 decrease from baseline at week 12 of treatment.
Results •
Patients from applicable trials (N > 2000) were HCV monoinfected or HIV-HCV
coinfected.
•
Patients
were treated with pegylated interferon alfa-2b (1.0 or 1.5 mcg/kg/week or 50-150
mcg/wk) and various doses of ribavirin (800-1400 mg/day).
•
Treatment
duration was 48 or 24 weeks, generally depending on genotype.
•
Attaining
RVR was highly predictive of attaining SVR in patients with any genotype who were
treated for 48 weeks (PPV 89%), in genotype 1 or 4 patients treated for 48 weeks
(PPV 81%), and in genotype 2 or 3 patients treated for 24 weeks (PPV 85-90%).
•
Not
attaining RVR was a less reliable predictor of failure to attain SVR for all genotypes
(NPV 59%).
•
NPVs
were 84% among genotype 1 or 4 patients and 44%-63% among genotype 2 or 3 patients.
•
Genotype
2 or 3 patients were analyzed separately in 1 study; the PPV and NPV for RVR were
89% and 50%, respectively, for genotype 2 patients and 100% and 57%, respectively,
for genotype 3 patients.
•
Studies
in genotype 4 patients revealed NPVs for EVR of 86%-100% and PPVs for EVR of 76%-100%.
•
Failure
to attain EVR was a consistent indicator of failure to attain SVR (NPV 95%-100%),
whereas attaining EVR was a less reliable predictor of attaining SVR (PPV 67%-72%)
for all genotypes.
•
Among African Americans, NPVs and PPVs for EVR were 100% and 48%-83%, respectively.
Based
on these results, the study authors concluded: •
EVR was a better negative
than positive predictor of SVR and can be used to guide decisions about treatment
cessation in genotype 1 or 4 patients who do not respond by week 12 of treatment.
•
RVR was an excellent
positive predictor but poor negative predictor of SVR for all genotypes.
•
RVR can be used as
a patient motivator and can reliably be used as part of the treatment algorithm
for future studies and in clinical practice.
Cedars-Sinai
Medical Center, Los Angeles, CA; Schering-Plough Corporation, Kenilworth, NJ. 11/06/07 Reference
F Poordad and C Kambili. Predictability of Response: Positive and Negative
Predictive Values of Rapid and Early Virologic Responses to Peginterferon alfa-2b
and Ribavirin in the Treatment of Chronic Hepatitis C. 58th Annual Meeting of
the American Association for the Study of Liver Diseases. Boston, MA.
November 2-6, 2007. Abstract (poster) 305.
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