Final Results of the Canadian Pegylated Interferon Alfa-2b (PegIntron) Prospective Optimal Weight-based Dosing Response (POWeR) Study

By Ronald Baker, PhD

Researchers designed the POWeR study (Peginterferon alfa-2b Prospective Optimal Weight-based Dosing Response) to determine the impact of hepatitis C virus (HCV) genotype, baseline viral load, weight, and fibrosis stage on sustained virological response (SVR) rates in treatment-naive patients with chronic hepatitis C who were treated with pegylated interferon alfa-2b (PegIntron) and weight-based ribavirin in a "real-life" observational setting.

Final Results were reported at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007).

POWeR was an open-label observational trial conducted in academic and community clinics across Canada between 2002 and 2006. All patients received pegylated interferon alfa-2b (1.5 mcg/kg/week) plus 800-1200 mg/day weight-based ribavirin for either 24 (genotypes 2 and 3) or 48 (genotype 1) weeks.

SVR -- defined as undetectable HCV RNA 24 weeks after completion of treatment -- was stratified by genotype, baseline viral load, and fibrosis score.

Results

• 1977 patients initiated treatment.

• Subjects were excluded if they had undetectable HCV RNA at the end of treatment but no 6-month follow-up, had no treatment data available, or had HIV-HCV coinfection.

• The analysis was based on 1800 patients, including those who discontinued treatment because of side effects, lack of response, or personal reasons.

• Most patients were infected with HCV genotype 1 (60%), followed by genotype 3 (22%) and genotype 2 (15%).

• 3% percent of patients had genotypes 4, 5, or 6 or no specified genotype.

• Baseline viral load was available for 1477 patients; 52% had high viral load (> 600,000 IU/mL or 2 x 106 copies/mL).

• Liver biopsy specimens were available for 946 patients (53%), revealing absent to moderate fibrosis (stage F0-F2) in 60% and advanced fibrosis or cirrhosis (stage F3-F4) in 40%.

• The SVR rates were higher in patients with minimal (F0-F2) fibrosis than in those with advanced (F3-F4) fibrosis/cirrhosis (60% vs 35%; P < 0.001).

• The SVR rate was higher in patients with low versus high baseline viral load (57% vs 50%; P = 0.009).

• Baseline viral load and fibrosis score were negative predictive factors for SVR in genotype 1 and genotype 3 patients, but not genotype 2 patients.

• Sustained virologic response (SVR) rates were observed in different weight groups in patients treated with weight-based PegIntron plus ribavirin.

• Patients with more advanced liver disease experienced lower SVR rates.

• Weight was not a cofactor in achieving SVR.

End-of-treatment (EOT), SVR, and
Relapse Rates Stratified by Genotype

* no genotype data available for 16 patients. ** P < 0.001

Based on these findings, the researchers concluded, "Excellent SVR rates and low relapse rates with pegylated interferon alfa-2b plus ribavirin may be attained in a real-life observational setting."

In addition, they noted, "Observational trials include a more heterogeneous patient population than those observed in controlled trials and provide useful information to practitioners and regulators on post-approval drug use."

London Health Sciences Centre, London, ON, Canada; Mount Sinai Hospital, Toronto, ON, Canada; University of Western Ontario, London, ON, Canada; Ottowa Hospital - Civic Campus, Ottowa, ON, Canada; Ontario Addiction Treatment Centers, Richmond Hill, ON, Canada; Hamilton Health Sciences General Site, Hamilton, ON, Canada; Centre Sida Amitié des Laurentides, St. Jerome, QC, Canada; University of Alberta, Edmonton, AB, Canada; Private Practice, Vancouver, BC, Canada; Schering-Plough Canada Inc, Pointe Claire, QC, Canada; Royal Alexandra Hospital, Edmonton, AB, Canada.

11/06/07

Reference
P Marotta, L Scully, M Varenbut, and others. Final Results of the Canadian POWeR (Peginterferon alfa-2b Prospective Optimal Weight-based Dosing Response) Program. Sustained Virologic Response (SVR) to Weight-Based Peginterferon alfa-2b + Ribavirin in a Large, Mixed Community and Academic Observational Study. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA. November 2-6, 2007. Abstract (poster) 254.