BOSTON – Anemia developed significantly more often among
patients with hepatitis C virus infection and compensated cirrhosis than among
noncirrhotic patients during triple therapy in a randomized, open-label trial of
treatment-naive patients, but in most instances the anemia was effectively
treated.
In an anemia management subanalysis of a study comparing
sustained virologic response (SVR) rates in cirrhotic and noncirrhotic patients
treated with boceprevir (Victrelis), pegylated interferon alfa-2b (Peg-Intron),
and ribavirin (RBV), 57% of patients with cirrhosis and anemia treated with a
ribavirin dose reduction had an SVR, compared with 64% of those treated with
erythropoietin. Among noncirrhotic patients with anemia, the respective SVR
rates were 73% and 72%; none of the differences was significant, Dr. Eric J.
Lawitz reported at the annual meeting of the American Association for the Study
of Liver Diseases.
 |
Courtesy US. Dept of Veterans Affairs
"Sustained viral responses are comparable in cirrhotic patients when anemia is managed by ribavirin dose reduction or erythropoietin," said Dr. Eric J. Lawitz. |
"Sustained viral responses are comparable in cirrhotic
patients when anemia is managed by ribavirin dose reduction or erythropoietin,"
said Dr. Lawitz, medical director and principal investigator at Alamo Medical
Research in San Antonio, Tex., adding that ribavirin dose reductions should be
the initial strategy for managing anemia, followed, if necessary, by
erythropoietin.
In the trial, 687 treatment-naive patients with hepatitis C
virus (HCV) infections were treated for 4 weeks with pegylated interferon
(PEG-IFN) alfa-2b and RBV, then 24 or 44 weeks of boceprevir added in. Baseline
hemoglobin levels ranged from 12 g/dL to15 g/dL for women, and from 13 g/dL to15
g/dL for men.
Patients with a hemoglobin level approaching 10 g/dL or less
(tested from baseline through week 48) were randomized to either ribavirin dose
reduction (249 patients) in 200-mg increments (first increment of 400 mg for
initial 1,400-mg daily doses) at the investigators’ discretion, or to
erythropoietin (251 patients) at 40,000 U/wk, modifiable to 20,000 U/wk or
60,000 U/wk at the investigator’s discretion. The remaining patients received
anemia prophylaxis but were not randomized.
If the hemoglobin level dropped to 8.5 g/dL, patients could
receive the other treatment as a secondary intervention, and patients with a
hemoglobin level of 7.5 g/dL were discontinued from all study drugs.
Primary efficacy measures for all patients (cirrhotic and
noncirrhotic) in each anemia strategy group were identical, with 82% having an
end-of-treatment response, 71% having an SVR, and 10% experiencing relapse.
Among cirrhotic vs. noncirrhotic patients, rates were 68% vs.
76% for end-of-treatment response , 55% vs. 64% for SVR, and 18% vs. 11% for
relapse.
Patients with cirrhosis were significantly more likely to
require a secondary anemia intervention (44% vs. 26%, P = .009). Among
noncirrhotic patients (but not cirrhotic patients), a secondary anemia
intervention was associated with a greater likelihood of SVR (80% vs. 70% for
only one intervention, P = .05).
Serious adverse events occurred in 20% of cirrhotic patients
and 12% of noncirrhotic patients, but only one study death occurred. The
noncirrhotic patient died of a cardiac arrest, which was considered to be
unrelated to therapy.
Treatment-emergent adverse events occurred in 3% of patients
with cirrhosis and 2% of those without cirrhosis. Drug discontinuation for
adverse events occurred in 17% of cirrhotic patients, and 16% of noncirrhotic
patients.
Cirrhotic patients were more likely to have hemoglobin
concentrations ranging from 6.5 to 8.0 g/dL than were noncirrhotic patients, but
no patient in either group had a hemoglobin concentration below 6.5 g/dL.
Neutrophil counts in the range of 500-749/mm3
occurred in 24% of cirrhotic patients and 27% of noncirrhotic patients, and
counts below 500/mm3 were seen in 20% and 12%.
Platelet counts from 25,000 to 49,999/mm3 occurred
in 22% of cirrhotic patients and 2% of noncirrhotic patients. Counts below
25,000/mm3 were seen in 3% vs. less than 1%, respectively.
Transfusion rates were similar between the groups.
The study was funded by Merck Sharp & Dohme, which
manufactures boceprevir. Dr. Lawitz disclosed receiving grant and research
support from the company.
No comments:
Post a Comment