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More on the HALT-C Trial: 4-year study of Maintenance Therapy in 1350 patients
Written for NATAP by Mark Sulkowski, MD, Johns Hopkins University School of Medicine
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Abstract 279. Retreatment of Interferon And Interferon-Ribavirin
Non-Responders with Peginterferon-alpha-2a (Pegasys) And Ribavirin: Initial
Results from the Lead-In Phase of the Halt-C Trial
The HALT-C trial was designed to determine if long term maintenance
interferon therapy, administered over 4 years, could prevent histologic
progression, reduce the development of hepatocellular carcinoma and the need
for hepatic transplantation in patients with chronic HCV and advanced
fibrosis or cirrhosis who remain HCV-RNA (+) despite therapy. Since
peginterferon plus ribavirin is more effective than standard
interferon/ribavirin for treatment of chronic HCV all patients enrolled in
the HALT-C trial were first treated with peginterferon plus ribavirin during
the lead-in phase of this trial.
This study is enrolling 1350 patients with advanced liver disease (bridging
fibrosis/cirrhosis, Ishak Fibrosis stage > 3) and no evidence of hepatic
decompensation. All patients had previously failed to respond to
interferon-based therapy administered for at least 12 weeks. After
screening, all patients received pegylated interferon alfa-2a (180 mcg
weekly) plus ribavirin (1 - 1.2 grams/day). Patients who are HCV-RNA (-) at
week 20 continue therapy for 48 weeks total. Patients who are HCV-RNA (+)
either stop treatment or receive a maintenance dose of Pegasys 90ug/week for
3.5 years.
Dr. Adrian Di Bisceglie presented on-treatment virologic response data on the
first 268 patients who completed at least 20 weeks of therapy within this
ongoing study. For the purpose of this presentation, viral response was
defined as an undetectable HCV-RNA level at treatment week 20. 15 (5.6%)
patients discontinued therapy prior to week 20. At week 20, 107 of 268
patients (42%) (based on an intention-to-treat analysis) had an undetectable
HCV RNA level. These patients will continue therapy for an additional 28
weeks and, per protocol, will not enter the "maintenance" phase of the study.
There were several important "sub-group" analysis presented. Persons who
had only failed prior interferon monotherapy were much more likely to achieve
a response than those who failed prior interferon/ribavirin combination
therapy (53% > 31%) and African-Americans were significantly less likely to
respond than others (10% < 43%).
In addition, a large number of patients had dose reductions of the
PEG-interferon (53%), ribavirin (44%) or both (47%). Thus, while the
discontinuation rate was quite low (~5%), it remains uncertain if such dose
reductions will impair the overall effectiveness of the therapy.
Nonetheless, these results are encouraging and suggest that persons with
advanced liver disease who failed to respond virologically to prior therapy
may benefit from a course of pegylated interferon/ribavirin.
Editorial note: Baseline data for 268 patients-- 41% of patients in study had
cirrhosis at baseline. 84% were genotype 1. Mean ALT was 124. 88% were
Caucasian. 63% had received IFN+RBV. Mean HCV-RNA was 3.5 million IU/mL. Mean
age 50. The degree of fibrosis was associated with response (44% Ishak 3-4
[bridgng fibrosis] vs 31% Ishak 5-6 [cirrhosis], p=0.03). Gender was not
associated with response (40 vs male vs 36% female, NS). Genotype was a
factor in response Genotype 2b: 88%; genotype 3a: 93%, genotype 1a: 30%;
genotype 1b: 39%; genotype 2a: 35%. Baseline HCV-RNA did not appear to
influence response. Mean reduction in HCV-RNA was 3.7 log; 45% had a 3+ log
reduction, while 15% had a 2-log reduction, 21% had a 1-log reduction, and
18% had <1-log reduction. It will be interesting to see if the patients with
little viral load reduction demonstrate improved, stopped, or slowed
fibrosis.
The long-term goals or outcomes from HALT-C will take several years to
achieve. These interim results are similar to those seen in several other
smaller studies reported at the conference.
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