Early
Predictors of Anemia in Genotype 1 HCV Patients Treated with Pegasys plus
Adherence
to standard ribavirin dosing is critically important to achieving sustained
virological response (SVR) in the treatment of chronic genotype
1 hepatitis C virus (HCV) infection. However, higher ribavirin doses can cause
hemolytic anemia in this patient population.
In
studies with pegylated interferon plus ribavirin, hematologic abnormalities were
common: hemoglobin (Hgb) level < 12 g/dL in 52% of pts and Hgb < 10 g/dL
in 13%. Also, ribavirin dose reduction was required in 22% of patients receiving
combination therapy for 48 weeks.
However,
pre-treatment predictors of considerable anemia (defined as a Hgb decrease >
2.5 g/dL from baseline) were inadequate to guide therapeutic intervention.
Analysis
of 59 genotype patients showed that a Hgb decrease > 1.5 g/dL from baseline
at week 2 significantly correlated with ribavirin at week 4. Thus, to test the
predictive value of week 2 Hgb drop, the authors of the present study analyzed
data from 2 prospective, randomized, Phase III trials of pegylated
interferon alfa-2a (Pegasys) plus ribavirin [NEJM 2002;347:975; Annals Internal
Med 2004;140:346].
The
researchers analyzed baseline characteristics (gender, race, age, bodyweight,
BMI, fibrosis, genotype, Hgb, platelets, white blood cell count, creatinine, creatinine
clearance, week 2 Hgb drop ? 1.5 g/dL, and ribavirin and Pegasys doses) of 555
genotype 1 patients receiving Pegasys 180 mcg/week plus ribavirin 1-1.2 g/d for
48 weeks, to determine their predictability for considerable anemia at week 4
using univariate and multiple logistic regression analyses.
Results
Significant factors associated with considerable anemia at week 4 in 236 patients
exhibiting a ? 2.5 g/dL decrease in Hgb are listed in the table below.
Considerable anemia at week 4 was also significantly associated with more or earlier
drug dose reductions due to anemia (P < 0.0001) and lower cumulative dose of
ribavirin (P < 0.001).
The SVR rates in patients with considerable anemia at week 4 was only marginally
reduced compared with non-anemic patients (47.5% vs 51.7%, respectively).
Factors associated with considerable anemia at week 4
Univariate
Multivariate
P-value
Odds ratio (95% CI)
Age (10 yrs)*
<0.001
ns
–
Gender (female vs male)
0.0426
ns
–
Race (Black/Asian vs other)
0.0046
0.0035
0.31 (0.14–0.68)
Baseline Hgb (1 g/dL)*
<0.0001
0.0087
1.34 (1.08–1.66)
CLR (10mL/min)*
<0.0001
0.0003
0.82 (0.73–0.91)
Cirrhosis (present vs absent)
0.0808
0.0121
2.06 (1.17–3.61)
Wk 2 Hgb drop (≥ 1.5 g/dLvs other)
<0.0001
<0.0001
23.2 (14.1–38.1)
Pegasys exposure week 1–4
(1 mcg/wk/kg)*
0.0275
0.0293
1.77 (1.06–2.95)
*For continuous
variables, the odds ratio presented relates to a one-unit change (e.g. the odds
of having an Hgb drop of > 2.5g/dL in a patient with a baseline Hgb
of 11 g/dL is 34% higher than in a patient with an Hgb of 10g/dL)
Conclusion
Based
on the results, the authors concluded, "Important predictors of considerable
anemia at week 4 included a week 2 Hgb drop ? 1.5g/dL, non-Black/Asian race, and
cirrhosis."
"Patients
with a week 2 Hgb drop experienced more dose reductions and sub-therapeutic ribavirin
doses than those with no wk2 drop."
"Early
anemia intervention in patients with a week 2 Hgb drop > 1.5g/dL may avoid
ribavirin dose reduction, thereby improving the chance of achieving an SVR."
University
of Chicago, Chicago, IL; Henry Dunant Hospital, Athens, Greece; IST GmbH, Mannheim,
Germany; University of North Carolina, Chapel Hill, NC.
11/07/06
Reference D
Jensen, N Reau, S J Hadziyannis, and others. Early predictors of anemia in patients
with HCV genotype 1 treated with peginterferon alfa-2a (40KD) plus ribavirin 1000-1200
mg/day. 57th AASLD. October 27-31, 2006. Boston, MA. Abstract 395.
Significant factors associated with considerable anemia at week 4 in 236 patients
exhibiting a ? 2.5 g/dL decrease in Hgb are listed in the table below. 
