There
is a strong bias against admitting older patients into clinical trials of most
new drugs in development in the US, unless the therapy under study is specifically
targeted to that population. This bias also is present in studies of antiviral
therapies for chronic hepatitis C.
The
widespread prohibition of entry to older patients into clinical trials for hepatitis
C treatments is due in part to a concern about the ability of these individuals
to tolerate the adverse
effects (AEs) of peginterferon plus ribavirin, the standard of care for hepatitis
C. In addition, there is a widely held belief that older patients experience decreased
efficacy from peginterferon plus ribavirin.
Predictably,
as a direct result of the ineligibility of patients aged >65 for clinical trials
of anti-HCV drugs, there are very limited data on this patient population in regard
to response to therapy. The role of age in determining response to peginterferon-based
antiviral therapy for chronic HCV needs to be better defined.
The
objective of the current study, presented at the 57th AASLD in Boston, was to
determine if age is an independent predictor of sustained
virological response (SVR) or medication tolerability within a randomized,
controlled clinical trial of treatment-naïve HCV patients with HCV.
The
patient age groups studied were 18-25 yrs (n=69); 26-35 yrs (n=350); 36-45 yrs
(n=1866); 46-55 yrs (n=2200); 56-65 yrs (n=368); and >65 yrs (n=55).
In
this subanalysis of the WIN-R trial, patients were randomized to receive peginterferon
alfa-2b 1.5?g/kg/wk plus either ribavirin 800 mg/d or ribavirin 800 mg-1400mg/d
based on body wt. Patients with HCV genotype (G) 1 or 4 received 48 weeks of therapy
while those with G 2 or 3 were randomized to 24 or 48 weeks of therapy.
4913
pts. received at least 1 dose of medication and are included in this analysis.
Although patients aged >65 were ineligible, 55 individuals >65 years old
were enrolled as protocol exceptions. Logistic regression analyses of SVR comparing
two age categories were performed.
Results
The overall SVR was 44%.
SVR rates for the age groups were: 18-25 = 57%, 26-35 = 41% (p=0.02 vs 18-25),
36-45 = 44% (p=0.03 vs 18-25), 46-55 = 42%, 56-65 = 40% (p=0.01 vs 18-25) and
for >65 SVR = 45%.
There was no difference in SVR in any other patient age groups including those
aged >65.
There were no differences in serious adverse events (SAEs) between all age groups.
Patients
aged 26-35, 36-45 and 46-55 had fewer AEs than those in the 56-65 and the >65
groups. Treatment
discontinuations were significantly higher among the 26-35 yrs. group when compared
to two groups, but there was no difference in the treatment discontinuations in
the >65 yrs. group compared with any other.
Based
on these findings, the authors conclude the following:
Adults aged 18-25 yrs had significantly increased chances of obtaining SVR than
most other age groups.
Patients >65 had similar SVR to all other age groups.
Although there were more AE's in the older age groups, the rate of SAE's was the
same and treatment drop-outs were the same or less than the younger age groups.
Patients
should not be denied antiviral therapy based upon age alone.
Northwestern
University, Chicago, IL; Weill Medical College of Cornell University, New York,
NY; Columbia University College of Medicine, New York, NY; Baptist Medical Center,
Kansas city, MO; Beth Israel Deaconness Medical Center, Boston, MA; Indiana University
School of Medicine, Indianapolis, IN; Atlantic Gastroenterology, Egg Harbor Township,
NJ; Austin Gastroenterology, PA, Austin, TX; California Pacific Medical Center,
San Francisco, CA; Indianapolis Gastroenterology, RSCH, Indianapolis, IN; Schering
Plough Research Institute, Kenilworth, NJ.
The overall SVR was 44%. 
