Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
EVALUATING VIROLOGIC RESPONSE WITHIN 2-4 WEEKS HAS HIGH POSITIVE/NEGATIVE PREDICTIVE VALUES FOR SUSTAINED VIROLOGIC RESPONSE IN PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C DURING TREATMENT
A. Neumann1,2*, M. Shiffman3, P. Ferenci4, G. Foster5, E. Yoshida6, S. Pianko7, M. Sulkowski8, S. Zeuzem9, Y. Benhamou10, D. Nelson11, J. McHutchison12, E. Pulkstenis13, G. Subramanian13, for the ACHIEVE Study Group
1Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel, 2Institute for Theoretical Biology, Humboldt University, Berlin, Germany, 3Virginia Commonwealth University Medical Center, Richmond, VA, USA, 4Medical University of Vienna, Vienna, Austria, 5The Royal London Hospital, London, UK, 6University of British Columbia, Vancouver, BC, Canada, 7Monash Medical Centre, Clayton, VIC, Australia, 8Johns Hopkins Center for Viral Hepatitis, Baltimore, MD, USA, 9J.W. Goethe-University Hospital, Frankfurt/Main, Germany, 10Hôpital Pitié-Salpêtrière, Paris, France, 11University of Florida, Gainesville, FL, 12Duke Clinical Research Institute, Durham, NC, 13Human Genome Sciences, Inc., Rockville, MD, USA. *email@example.com
Background and aims: Knowing the positive/negative predictive values (PPV/NPV) of SVR as early as possible during CHC treatment allows for better patient management. Albinterferon alfa-2b (albIFN) is a novel, long-acting, fusion polypeptide that is dosed every 2 weeks. This study validated a previously identified prediction algorithm that allows high positive prediction as early as 2 weeks and high negative prediction as early as 4 weeks after starting therapy.
Methods: 1323 patients were randomized to peginterferon alfa-2a 180 µg/wk, or albIFN 900 or 1200 µg q2wk, all with weight-based ribavirin 1000-1200 mg/d, for 48 weeks. HCV RNA was measured by real-time PCR (lower limit of detection 15 IU/mL; limit of quantitation 43 IU/mL). A prospectively defined positive and negative prediction algorithm at treatment weeks 2-4 was compared with rapid virologic response at week 4 and no early virologic response at week 12 in the per-protocol population (n=747). Since noninferiority in SVR rates (56%-59%) and similarity of early predictive parameters among all arms were established, data were pooled for the prediction analysis (n=747). Results were similar for the ITT population.
Results: Rapid initial virologic response at week 2 (viral decline >2 log10IU/mL) was observed in 34% of patients, with a high PPV (92%) for SVR. This early week-2 algorithm applied to more patients and compared favorably with rapid virologic response found in 26% of patients (PPV 98%). No initial virologic response at week 4 (viral decline < 2 log10IU/mL; viral load >5.5 log10IU/mL), found in 14% of patients, demonstrated a high NPV (96%) with 33% specificity. This early endpoint compared favorably with no early virologic response observed 8 weeks later at week 12 (NPV 98% in 14% of patients). A sequential prediction algorithm based on viral kinetics at weeks 2 and 4 reliably predicted treatment outcome in 67.5% of patients significantly earlier than week 12.
Conclusions: Using early viral kinetics information, it is possible to achieve both a high PPV and NPV for SVR as early as treatment weeks 2-4. Identifying early predictors of on-treatment response is important for tailoring response-guided therapy in the future with direct antiviral CHC therapy.