A new form of pegylated interferon is
associated with significantly fewer side-effects than the standard form of the
drug, a study conducted in patients with the easier-to-treat hepatitis C
genotypes shows.
Data from the EMERGE phase IIb study
presented to the 47th International Liver Congress (EASL
2012) in Barcelona demonstrated that pegylated interferon-lambda was as effective
as pegylated interferon alpha. The major advantage of the new compound was that
it caused significantly fewer side-effects. Interferon lambda or alpha was
taken in combination with ribavirin. Another key finding of the study was that
there were fewer dose reductions of both interferon and ribavirin with the
lambda-based combination.
A number of drugs which work directly
against hepatitis C have been approved or are in development. However, for the
foreseeable future these will need to be taken in combination with pegylated
interferon and ribavirin. The side-effects associated with these two drugs are
a major limitation of hepatitis C therapy. Therefore a more tolerable form of inteferon would be advantageous in order to allow more patients to start and complete therapy and to achieve a cure.
Glossary
- neutropenia
A shortage of neutrophils, a type of white blood
cell that fights bacterial infections.
Preliminary
research has shown that pegylated interferon-lambda is as effective as
interferon-alpha but has a benign side-effect profile when used for the
treatment of hepatitis C genotype 1.
Investigators conducted further research to assess the efficacy and
tolerability of this new form of pegylated interferon in patients with
genotypes 2/3.
A
total of 118 treatment-naive patients
were recruited to the study. Therapy lasted for 24 weeks. Treatment responses
up to 24 weeks post-completion of treatment were assessed. An undetectable
hepatitis C viral load at week 24 was defined as a sustained virological
response.
None of the patients had cirrhosis and they
were randomised in equal proportions into four treatment arms. Individuals in three of the arms were
treated with a weekly dose of pegylated interferon-lambda (120, 180 or 240 μg) plus ribavirin.
Patients in the fourth arm received pegylated interferon-alpha and ribavirin
and served as controls.
There were no significant baseline differences between the
treatment arms.
Rates of sustained virological response for the lambda-treated
patients ranged between 57% and 83%. The best results were seen for the 180 μg dose (genotype 2 = 71%; genotype 3 = 83%). These
compared to a response rate of between 40% and 67% for patients in the control
arm.
In most respects, interferon-lambda had a superior safety profile
to interferon-alpha. An interferon dose reduction was necessary for between 7%
and 13% of the lambda patients (180 μg = 7%) compared to 27% of those treated
with interferon-alpha.
None of the patients taking the lambda formulation needed to
reduce their dose of ribavirin because of low haemoglobin. However, a ribavirin
dose reduction was necessary for 23% of the patients taking interferon-alpha.
Flu-like symptoms developed in between 17% and 23% of those
treated with interferon-lambda. This compared to a rate of 40% for patients in
the control arm.
Musculoskeletal symptoms also occurred less frequently in the
lambda-treated patients than in those treated with interferon-alpha (17% to 28%
vs 63%).
Fatigue was reported by 50% of patients treated with the 240 μg
dose of lambda, by 28% of those on the 180 μg dose and by 41% of individuals in
the 120 μg arm. This compared to a prevalence of 53% among the alpha-treated
patients.
Overall, approximately 9% of patients in the lambda study arms
developed anaemia, compared to a prevalence of 45% in the control arm. None of
the patients treated with lambda developed either neutropenia or a low platelet
count. This compared to rates of 52% and 24% respectively in the alpha-treated
patients.
ALT or AST elevations five or more times higher than the upper
limit of normal developed in 3% of patients treated with the 240 μg lambda dose.
None of the other lambda doses were associated with these abnormalities in
liver function, and this was also the case for interferon-alpha. Elevated
bilirubin was seen in 7% of patients treated with the highest lambda dose. None
of the other lambda doses or interferon-alpha caused this disturbance.
In some other respects the safety profiles of lambda and alpha interferon
were similar. Most notably both drugs were equally likely to cause
neuropsychiatric side-effects (lambda prevalence = 40-44% vs 33% alpha).
A press release issued by the manufacturer BMS stated that the
results suggested that lambda had the potential to meet unmet needs of
hepatitis C-infected patients and that the data supported further investigation
of the compound.