Viral Load at Week 12 and Reduction in Viral Load in First 12 weeks of Therapy is Useful in Predicting Response

Clinical Utility of HCV RNA Quantification Using the Test as an Early Predictor of Sustained Response (AASLD abstract 802)
Mitchell L. Shiffman, Medical College of Virginia, Richmond, VA, et al.

This analysis was designed to determine whether quantification of HCV RNA (COBAS AMPLICOR HCV MONITOR) prior to and during the first 16 weeks of therapy, with either PEG(40kDa) IFN -2a (PEGASYS ®) or unmodified IFN -2a, could be used to predict sustained virological, biochemical, and histological responses. Data were obtained from 122 patients involved in a randomized, open label study who received PEG(40kDa) IFN -2a (45, 90, 180, or 270 µg) or IFN -2a for 48 weeks. HCV RNA levels at weeks 8, 12, and 16 were highly predictive of sustained virological response and sustained biochemical response, and to a lesser extent, histological response. The lower the HCV RNA level during the first 16 weeks of treatment, the greater the likelihood that the patient ultimately achieved a sustained response after the cessation of therapy. For example, patients who had HCV RNA levels of <10 5 , <10 4 , and <10 3 copies/mL at week 12 were, respectively, 29-, 39-, and 50-fold more likely to achieve a sustained virological response than patients with HCV RNA levels above these values. Similar results were obtained at the other timepoints and for predicting the likelihood of achieving a sustained biochemical response. Baseline HCV RNA levels were somewhat less predictive of response than were levels during the first 16 weeks of therapy. These data suggest that quantification of HCV RNA levels at 8, 12, and 16 weeks of therapy can be used to predict a sustained response among patients receiving either PEG(40kDa) IFN -2a or unmodified IFN -2a, and may be used to individualize therapeutic regimens. "These data suggest that quantification of HCV RNA levels at 8, 12, and 16 weeks of therapy can be used to predict a sustained response among patients receiving either PEG(40kDa) IFN -2a or unmodified IFN -2a, and may be used to individualize therapeutic regimens."

Prognostic Factors and Early Predictability of Sustained Viral Response in Patients Treated with PEG(40kDa) IFN -2a (PEGASYS) (AASLD abstract 803)
K. Rajender Reddy, University of Miami School of Medicine, Miami, FL, et al.

This study was designed to determine whether the dynamics of the viral response to therapy with PEG(40kDa) IFN -2a (PEGASYS) are similar to those reported for IFN -2a monotherapy and IFN -2a plus ribavirin combination therapy. Data from 3 large phase III trials involving 814 patients treated with PEG(40kDa) IFN -2a were analyzed. A stepwise logistic regression model was developed to identify baseline factors associated with sustained virological response. Viral measurements for all studies were analyzed using the COBAS AMPLICOR™ HCV test (lower limit of detection = 50 IU/mL) for qualitative measure, and the COBAS AMPLICOR HCV MONITOR™ for measurement of viral levels. The results indicate that baseline prognostic factors associated with a sustained response (ie, genotype, viral load, age, weight, and fibrosis stage) are similar to those previously reported for other therapies. In addition, similar to what has been reported in hepatitis B, the prognostic value of pretreatment necroinflammatory markers was reported for the first time. A baseline histology activity index (HAI) score >10, or an alanine aminotransferase level more than 3 times the upper limit of normal, were predictive for response.

"Patients on PEG(40kDa) IFN -2a who did not achieve an undetectable virus or a viral decline of 2 log from baseline had only a 2% probability of achieving a sustained virological response (ie, 0.98 negative predictive value)." Based on an intent-to-treat analysis among 564 patients who received PEG(40kDa) IFN -2a, the positive predictive value for achieving a sustained virological response for either an undetectable HCV RNA level (<100 copies/mL) or a 2-log drop in viral load from baseline was 0.45. However, the negative predictive value of this parameter was much higher. Patients on PEG(40kDa) IFN -2a who did not achieve an undetectable virus or a viral decline of 2 log from baseline had only a 2% probability of achieving a sustained virological response (ie, 0.98 negative predictive value).

The authors concluded that it is possible to reliably predict patients who have a very low likelihood of sustained viral response to PEG(40kDa) IFN -2a as early as week 12.

"Delayed Responders" Revisited: A Low Viral Load at Week 12 Predicts Sustained Responders to IFN -2b/Ribavirin Therapy (AASLD abstract 821)
Leland J. Yee, University of Alabama Liver Center, Birmingham, AL, et al.

This study examined whether viral load after 12 weeks of treatment with IFN -2b plus ribavirin combination therapy is predictive of sustained virological response among patients who had a delayed response (ie, decreased but detectable HCV RNA levels at week 12). HCV RNA was measured at weeks 12 and 24 during therapy, and at 24 weeks after the end of therapy among 47 patients with a delayed response. All were treated for 48 weeks if they had undetectable HCV RNA at week 24. "RNA levels at week 12 are useful in guiding treatment decisions among patients receiving IFN -2b plus ribavirin." Among 34 patients who had a week 12 viral load of <10,000 copies/mL, 14 (41%) achieved a sustained virological response. In contrast, none of the 13 patients with a 12-week viral load >10,000 copies/mL achieved a sustained virological response. The authors concluded that HCV RNA levels at week 12 are useful in guiding treatment decisions among patients receiving IFN -2b plus ribavirin. In particular, week 12 viral levels should be useful in deciding if treatment that is prescribed solely for elimination of HCV RNA should be continued.