Induction with High-dose Pegylated Interferon alfa-2a (Pegasys) Is More Effective than Standard Dosing for Achieving Rapid and Early Virological Response: The CHARIOT Study

The CHARIOT study, presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA (November 2-6, 2007), evaluated the efficacy and safety of a high-dose (360 mcg/week) pegylated interferon alfa-2a (Pegasys) induction regimen compared to standard therapy of 180 mcg/week Pegasys in combination with ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C

Australian researchers reported results of the planned interim analysis of the on-treatment virological responses over the first 12 wks of therapy in patients enrolled in the CHARIOT study.

In this international, multi-center, open label study, patients were stratified by baseline HCV RNA and randomized 1:1 to receive 180 mcg or 360 mcg Pegasys once weekly for 12 weeks followed by an additional 36 weeks of 180 mcg Pegasys. All also received 1000-1200 mg/day ribavirin for 48 wks. Endpoints included virological response at weeks 4, 8, and 12.

Results

• 845 patients were able to be evaluated for the efficacy and safety analysis.
  
  
• Age, sex, body weight, body mass index (BMI), race/ethnicity, HCV viral load, and liver fibrosis scores were similar in the 2 groups.
  
  
• At weeks 4, 8, and 12, virological response rates were greater (P<0.001) in the 360 mcg/week arm (see table below).
  
  
• Significantly higher response rates (P<0.001) at week 12 were observed in patients receiving the 360 mcg Pegasys induction dose in all subgroups including those with baseline HCV RNA ≥ 800,000 IU/mL (71% vs 55%) and < 800,000 IU/mL (84% vs 71%), body weight ≥ 85 kg (74% vs 56%) and < 85kg (74% vs 62%), and age > 40yrs (70% vs 54%) and ≤ 40yrs (84% vs 73%).
  
  
• Pegasys induction therapy was associated with higher rates of diarrhea (17% vs 12%), fever (14% vs 8%), chills (14% vs 7%), and weight loss (10% vs 3%).
  
  
• Reported incidence of depression and fatigue were similar in the 2 groups.
  
  
• Rates of treatment discontinuation were similar in both groups; however, induction therapy led to more dose modifications (see table).
  
  
• Use of hematopoetic growth factors was the same in both groups (4 patients [<1%]). 

Conclusion

Based on these interim findings, the researchers stated that induction dosing with 360 mcg/week pegylated interferon alfa-2a “is more effective than standard 180 mcg/week dosing in achieving early and rapid virological responses and is safe and well tolerated.”

“The effect was independent of baseline viral load, weight, BMI, and age,” they added.

Alfred Hospital, Melbourne, VIC, Australia; Nepean Hospital, Sydney, NSW, Australia; Greenslopes Hospital, Brisbane, QLD, Australia; Royal Perth Hospital, Perth, WA, Australia; Monash Medical Centre, Melbourne, VIC, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia; St. Vincent's Hospital, Melbourne, VIC, Australia; Roche Products, Sydney, NSW, Australia; Roche, Nutley, NJ, USA; National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW, Australia.

11/20/07

Reference
S Roberts, MD Weltman, D Crawfod, and others. Rapid and early virological response rates are increased with 12 week 360 mcg/wk peginterferon alfa-2a (40KD) and standard ribavirin in HCV genotype 1 treatment naive patients: efficacy and safety analysis of the induction phase of the CHARIOT study. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA. November 2-6, 2007. Abstract 54.