In
the EPIC3 program, researchers designed a large, prospective, controlled clinical
trial to assess the safety and efficacy of re-treatment with peginterferon
alfa-2b (PegIntron) and ribavirin (RBV) of these patients. The study authors
have previously reported a surprisingly high SVR in these patients, especially
those with an early viral response.
The
primary objective of this trial was to define early viral response at week 12
as a predictor of SVR in these patients.
HCV
non responders (NRs) or those that had relapsed following prior treatment with
I/R who had significant fibrosis (Metavir F2-F4) received PegIntron 1.5 microgram/kg
subcutaneously once weekly plus Rebetol 800-1400 mg/day for up to 48 weeks.
All
patients had pre-treatment biopsies scored by a single reviewer using METAVIR
criteria. Plasma HCV-RNA was determined at weeks 12, 24 and 48 of therapy and
FU 12 and 24 using a quantitative Taq-Man assay (SPRI; sensitivity 29 IU/mL).
Results
23% of the first 1354 patients treated in the combination therapy trial achieved
SVR.
Of those who attained > 2 log decrease in viral load at week 12, 37% achieved
SVR: 56% of those who were HCV-RNA (-), but only 6% of those who attained a 2
log decrease in HCV-RNA but remained HCV-RNA positive.
Of this latter group, 17% of subjects with very low viral load at TW12 (<100
IU) achieved SVR compared to 5% of those with residual viral load of >100-250
IU, and 0 in those with HCV-RNA >750.
Based
on these results, the authors conclude, "SVR is strongly correlated with
a negative HCV-RNA or HCV-RNA near the lower limit of detection at week 12, but
is extremely low in those with HCV-RNA >100 IU/ml."
"These
data suggest that undetectable viral load at week 12 (<29 IU/ml) best defines
a robust EVR that predicts SVR for previous I/R treatment failures re-treated
with PegIntron plus weight-based dosing of ribavirin."
Rate
of SVR based on Viral Load at Week 12 of Treatment
HCV-RNA
at TW 12 (I.U./mL)
SVR
% (n/total)
>750
0/582)
>500-750
4.8 (1/21)
>250-500
5.1 (2/39)
>100-250
5.1 (2/39)
29-100
6.9 (13/77)
Undetectable
56.1 (281/501)
Hopital
La Pitie Salpetriere, Paris, France; University of Miami School of Medicine, Miami,
FL, USA; Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo, Capital
Federal, Argentina; Hospital Universitario De La Princesa, Madrid, Spain; Northwestern
University, Chicago, IL, USA; VA Medical Center, Iowa City, IA, USA; Universiaetsklinikum
Charite-Campus Virchow, Berlin, Germany; Hospital Das Clinicas Da Unicamp, Campinas,
Brazil; University Health Network, Toronto Western Hospital, Toronto, ON, Canada;
Hospital General Universitario de Valencia, Valencia, Spain; Milton S. Hershey
Medical Center, Hershey, PA, USA; Elisabethinen Hospital of Linz, Linz, Austria;
Institut fuer klinische Pharmakologie, Bern, Switzerland; Hospital Provincial
Del Centenario, Rosario, Argentina; Hospital Universitario Gaffree & Guinle,
Rio de Janeiro, Brazil; Duke University Medical Center, Durham, NC, USA; Hospital
Universitario Austral, Pilar, Argentina; Service d'Anatomie Pathologique, Hopital
Beaujon, Clichy, France; Schering Plough Research Institute, Kenilworth, NJ, USA.
11/03/06
Reference T
Poynard, E Schiff, R Terg, and others. HCV RNA Negativity after 12 Weeks of Therapy
Is the Best Predictor of Sustained Viral Response (SVR) in the Re-Treatment of
Previous Interferon-a/Ribavirin Non-Responders (NR): Results from the EPIC3 Program.
57th AASLD. October 27-31, 2006. Boston, MA. Abstract 1123.
23% of the first 1354 patients treated in the combination therapy trial achieved
SVR. 
