Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
PREDICTING TREATMENT OUTCOME AMONG SLOW RESPONDERS: A RETROSPECTIVE ANALYSIS OF THE SUCCESS STUDY
M. Buti1*, V.G. Morozov2, V.V. Rafalskiy3, F. Wong4, J. Sumskiene5, X. Yu6, R. Faruqi6, L.D. Pedicone6, R. Esteban7
1Dept. of Internal Medicine - Hepatology, Liver Unit Hospital General Universitario Valle Hebron and Ciber-ehd del Instituto Carlos III, Barcelona, Spain, 2Hepatolog Medical Center, Samara, 3Smolensk State Medical Academy, Smolensk, Russia, 4Toronto General Hospital, Toronto, ON, Canada, 5Clinic of Gastroenterology, Kaunas, Lithuania, 6Schering Corp., a Division of Merck & Co., Kenilworth, NJ, USA, 7Liver Unit Hospital General Universitario Valle Hebron and Ciber-ehd del Instituto Carlos III, Barcelona, Spain. *email@example.com
Background: Several studies have examined a 72-week (wk) treatment duration with peginterferon plus ribavirin for patients with chronic hepatitis C (CHC) genotype 1 infection; however, there is no consensus regarding the subgroup of patients for which extended treatment should be considered.
Aim: To identify on-treatment predictors of sustained virologic response (SVR) in slow responders (≥2log decline in HCV RNA yet detectable at wk 12 and undetectable at wk 24) treated for 48 or 72 wks.
Method: This was an open-label, randomized, international study of patients with CHC genotype 1. Slow responders were randomized to receive peginterferon alfa-2b (1.5 µg/kg/wk) plus ribavirin (800-1400 mg/d) for 48 or 72 wks.
Results: 1,428 patients were enrolled of which 159 slow responders were randomized to 48 (n=86) or 72 wks treatment (n=73). SVR rates were 43.0% and 47.9% in 48 wk and 72 wk arms. Mean absolute HCV RNA levels at wk 4, 8, and 12 were similar in both arms. Change in HCV RNA at wk 4 was not predictive of SVR (Table). Among slow responders with < 2log decline at wk 8, SVR rates were 18.8% and 38.5% in 48 wk and 72 wk arms. Extended treatment did not improve SVR among slow responders with ≥2log decline at wk 8 or with ≥3log decline at wk 12; however, SVR was 25.0% and 46.7% in slow responders with 2-3log decline at week 12 when treated for 48 or 72 wks. Logistic regression revealed a weak association between week 8 viral load (≤2 versus >2log decline) and SVR (odds ratio = 2.504; 95% CI, 0.948 to 6.613; P = .064).
Conclusion: Slow responders with < 2log decline from baseline at wk 8, 2-3log decline at wk 12 and undetectable HCV RNA at wk 24 represent a group of patients who could benefit most from extended treatment.
[Table. SVR by decline in HCV RNA from baseline]
| ||Week 4 ||Week 8 ||Week 12 |
| ||<2 log ||≥2 log ||<2 log ||≥2 log ||2 to 3 log ||3 to 4 log ||≥4 log |
|48 wk arm ||27/66 (40.9) ||9/19 (47.4) ||3/16 (18.8) ||33/69 (47.8) ||4/16 (25.0) ||17/38 (44.8) ||16/32 (50.0) |
|72 wk arm ||29/58 (50.0) ||6/13 (46.2) ||5/13 (38.5) ||29/57 (50.9) ||7/15 (46.7) ||11/28 (39.3) ||17/30 (56.7) |