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Predictive
Factors for Dose Reduction and Treatment Discontinuation of Peginterferon
Alfa-2b in the Treatment of Chronic Hepatitis B
Treatment with interferon alfa has been shown to be effective in
one-third of hepatitis B e antigen-positive (HBeAg-positive)
chronic hepatitis B patients, but is clinically associated
with significant adverse events. In the
current study, Dutch researchers aimed to investigate the safety
of pegylated
interferon alfa-2b (PegIntron) in 300 hepatitis B e antigen-positive
patients with compensated liver disease.
Patients
were treated with pegylated interferon alfa-2b for 52 weeks combined
with either lamivudine
(Epivir-HBV) 100 mg/day or placebo. Pegylated interferon
alfa-2b was administered for 100 microgram once a week for 32 weeks;
thereafter, the dose was reduced to 50 microgram once a week.
Adverse
events and their effect on study medication were reported at monthly
visits in a standardized way.
Results
·
The
most frequently reported side-effects were flu-like syndrome (68%),
headache
(40%), fatigue
(39%), myalgia
(29%) and local reaction at the injection site (29%). These symptoms
typically occurred within the first month of therapy and subsided
during the course of therapy.
·
Neutropenia and thrombocytopenia
induced by pegylated interferon alfa-2b increased the risk
of infections and bleeding complications, but these complications
were rare and mild.
·
The
frequency of all side-effects was not different between patients
treated with pegylated interferon alfa-2b combined with lamivudine
or placebo.
·
In
69 (22%) patients the dose of pegylated interferon alfa-2b was reduced
prematurely. Of these dose
reductions, 36 (52%) were because of neutropenia.
·
Therapy
was discontinued in 28 (8%) patients.
·
The
most frequent reasons for early discontinuation were psychiatric side-effects
(depression, psychosis) and flu-like symptoms.
·
Multivariate
Cox regression analysis showed that low neutrophil count at baseline
and cirrhosis were independent predictors of dose reduction or therapy
discontinuation.
The
authors write in conclusion, “We conclude that in patients with
chronic hepatitis B and compensated liver disease prolonged pegylated
interferon alfa-2b therapy is safe, and that pre-existent cirrhosis
and neutropenia are the most important predictors of dose reduction
or early treatment discontinuation.”
Department of Gastroenterology and
Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam,
The Netherlands.
05/13/05
Reference
M
Zonneveld and others (for the HBV 99-01 Study Group). The safety
of pegylated interferon alpha-2b in the treatment of chronic hepatitis
B: predictive factors for dose reduction and treatment discontinuation.
Alimentary Pharmacology and Therapeutics 21(9):1163-71. May 2005.
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