Predictors
of Rapid and Early Virological Response to Pegylated Interferon
plus Ribavirin in Genotype 1 Hepatitis C Patients
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| SUMMARY:
Low pre-treatment HCV viral load, elevated ALT, normal
body weight, less severe liver damage, white race/ethnicity,
and adequate ribavirin dosage predicted favorable response
to treatment with pegylated
interferon plus ribavirin in an analysis of participants
in 5 American clinical trials that reflect the general
chronic hepatitis C patient population in the U.S.,
according to a report published in the February
2010 Journal of Viral Hepatitis. |
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By
Liz Highleyman
Maribel Rodriguez-Torres and colleagues performed a retrospective
analysis of data from prior studies of generally difficult-to-treat
patients, looking for baseline and on-treatment factors associated
with treatment response.
The
researchers looked at rates of rapid
virological response (RVR), or HCV RNA viral load clearance
at week 4 after starting therapy, and complete early virological
response (EVR), or undetectable viral load at week 12. Both of
these early responses predict sustained virological response (SVR),
or continued undetectable HCV RNA 24 weeks after completing of
treatment.
The
analysis included a total of 1550 HCV genotype 1 patients who
had been randomly assigned to receive 180
mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200
mg/day weight-adjusted ribavirin for 48 weeks in 5 clinical
trials. Among these trials, 3 were "enriched" with harder-to-treat
populations, including 1 study in which all 189 patients had high
baseline HCV viral load (> 800 000 IU/mL), 1 in which 74% of
participants were black (a group known to respond less well to
interferon), and 1 in which 47% were Latino, another group with
poorer
response rates compared with whites and Asians.
Results
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Overall,
15.6% of participants across studies achieved RVR and 54.0%
achieved complete EVR. |
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Baseline
factors that were significant predictors of RVR included: |
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Serum
HCV RNA 400 000 IU/mL (odds ratio [OR] 7.34); |
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Alanine
aminotransferase (ALT) level > 3 x upper limit of
normal (OR 2.01); |
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Not
having liver cirrhosis (OR 1.92); |
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Age
40 years (OR 1.56); |
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White,
non-Latino race/ethnicity (OR 1.41); |
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These
factors, along with body mass index 27 kg/m2, also predicted
complete EVR. |
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In
a multivariate analysis adjusting for these factors, a mean
on-treatment ribavirin dose > 13 mg/kg/day independently
predicted both RVR and complete EVR (OR 1.69 and 1.24, respectively). |
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Pegylated
interferon dose, however, was not a significant predictive
factor. |
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Blood
cell measures were also associated with early response (possibly
an indicator of drug doses, since ribavirin can cause anemia
and interferon can cause neutropenia, or low neutrophil count). |
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A
larger decrease in neutrophils was a significant predictor
of complete EVR but not RVR. |
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A
larger decrease in mean hemoglobin concentration (an
indicator of anemia) also predicted complete EVR but
not RVR. |
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In
conclusion, the investigators wrote, "several baseline and
on-treatment factors were associated with RVR and complete EVR
to peginterferon alfa-2a plus ribavirin in difficult-to-treat
HCV genotype-1 patients, providing important prognostic information
on the antiviral response in a patient cohort that is reflective
of the general chronic hepatitis C population."
"The
response to antiviral therapy in HCV-infected patients is heterogeneous
and, despite increases in SVR rates, treatment outcomes with peginterferon
alfa-2a plus ribavirin are not optimal in certain patient populations
and might still be improved," the researchers elaborated
in their discussion. "Monitoring the early antiviral response
to therapy can help identify those patients who are less likely
to achieve SVR and therefore provide critical information for
the overall management of patients with chronic hepatitis C."
"Optimizing
the antiviral response is crucial for accomplishing these goals,"
they continued. "Since ribavirin dose is one of the only
modifiable factors identified in this analysis that is associated
with an increase in RVR and complete EVR, physicians may be advised
to maintain a higher ribavirin dose to increase the likelihood
of achieving SVR."
Fundación
de Investigación de Diego, San Juan, Puerto Rico; Johns
Hopkins University, Baltimore, MD; Gastrointestinal Unit, Massachusetts
General Hospital, Boston, MA; Roche, Nutley, NJ; University of
Chicago, Chicago, IL.
4/9/10
Reference
M
Rodriguez-Torres, MS Sulkowski, RT Chung, and others. Factors
associated with rapid and early virologic response to peginterferon
alfa-2a/ribavirin treatment in HCV genotype 1 patients representative
of the general chronic hepatitis C population. Journal of Viral
Hepatitis 17(2): 139-147 (Free
full text). February 1, 2010.
