Pegetron Prospective Optimal Weight-based Dosing Response Program (POWeR): Preliminary Results

It has been suggested that obese patients with hepatitis C virus (HCV) have a more rapid progression of liver disease and lower rates of response to antiviral therapy than non obese patients.

Bodyweight was identified as an important predictor of sustained virologic response (SVR) among patients with chronic HCV infection in a pivotal clinical trial assessing the efficacy of peginterferon alfa-2b (PEG-IFN alfa-2b) [PegIntron] in combination with ribavirin (RBV).

Furthermore, weight-based dosing and mild hepatic fibrosis were Independently associated with achieving an SVR in a comparative study in patients with HCV genotype 1.

SVR was similar in obese and non obese patients who received weight-based PEG-IFN alfa-2b and RBV whereas SVR was lower in obese patients compared with non obese patients treated with fixed-dose PEG-IFN alfa-2a (Pegasys) plus RBV.

“In our trial,” write the study authors, “the impact of baseline bodyweight, HCV genotype and the level of fibrosis on HCV treatment outcome are determined in a community-based setting, providing “real-life” data.

The objectives of the current study were to determine the impact of bodyweight, HCV genotype and the level of fibrosis on virologic response in patients with chronic HCV infection when treated with a weight-based dosing regimen of PEG-IFN alfa-2b and RBV.

Patient Selection

Treatment-naοve patients (n=2,194) with chronic HCV were prospectively enrolled between December 2002 and December 2004, in this open label trial conducted in 160 academic and community clinics across Canada.

All patients were eligible for treatment with PEG-IFN alfa-2b and RBV (Pegetron, Schering-Plough Canada) according to criteria listed in the Pegetron Product Monograph

• At baseline, the following patient characteristics were recorded:

– bodyweight (<50kg, 50–<64kg, 64–<75kg, 75–<85kg, ≥85kg)

– HCV genotype (G1, G2, G3, or other)

– extent of fibrosis determined by liver biopsy (not all patients)

• none to mild (Metavir score 0–1)

• moderate (Metavir score 2)

• severe (Metavir score 3)

• cirrhosis (Metavir score 4).

•All patients received:

– PEG-IFN alfa-2b (PegIntron) 1.5μg/kg/week

– RBV 800–1,200mg/day (dependent on bodyweight).

• Patients received treatment for 24 weeks (non-G1) or 48 weeks (G1) based on treatment guidelines5 and standard of care.4

• In this community-based trial, patients were treated, followed and managed per current treatment guidelines, with no study-related intervention beyond collection of data.

Virologic Response

• An end-of-treatment (EOT) virologic response was defined as being HCV RNA negative after 24 weeks (non-G1) or 48 weeks (G1) of treatment.

• SVR was defined as being HCV-RNA negative at 24 weeks after the EOT.

• SVR rates were analyzed by baseline bodyweight, fibrosis level and HCV genotype.

• Further to this initial analysis, future reports will analyze data on relapse rate and prognostic indicators.

Results

Baseline Demographics

• Baseline demographics of the study population are shown in Table 1.

• Patient distribution by genotype within each weight group was similar, ranging from 48% to 52% for genotype 1 and 46% to 52% for genotypes 2/3.

• Over one-third of patients (36.6%) had severe or cirrhotic fibrosis (Metavir score F3 or F4), with 62.6% of patients having mild to moderate (F0–F2) levels of fibrosis.

• Patient distribution by baseline fibrosis level was similar within the lower weight groups (<50kg and 50kg–<64kg groups: F3/F4 = 25–26%).

+ However, as weight increased, an increasing number of patients had severe or cirrhotic fibrosis (64kg–<75kg group: F3/F4 = 33%; 75kg–85kg and ≥85kg groups: F3/F4 = 38%).

Virologic Response

• EOT response rate was 69% (775/1,120)

• Overall SVR rate was 66% (629/952) following weight-based dosing with PEG-IFN alfa-2b and RBV. Figure 1 shows SVR rates by weight distribution.

• PEG-IFN alfa-2b combined with RBV, administered as a weight-based dosing regimen, provided SVR rates of ≥62% (62.9–68.9%) in all weight groups, with no significant differences in SVR between the different weight groups.

• As expected, a higher percentage of patients with genotypes 2 or 3 achieved an SVR (85% and 78%, respectively) than patients with genotype 1 (52%).

• More patients with a baseline fibrosis level of F0–F1 or F2 achieved an SVR (76% or 68%, respectively) than patients with a severe fibrosis level (F3 or F4; 42% or 41%, respectively).

Conclusions

• Regardless of bodyweight, SVR rates were consistently high in patients treated with a weight-based dosing regimen of PEG-IFN alfa-2b and RBV.

• These findings are particularly encouraging given that this is a “real-life” community study with similar patient distribution by genotype within each weight group and a higher level of fibrosis in the heavier weight groups.

• Preliminary data from this community study indicates that genotype and fibrosis level influence SVR. Other baseline characteristics which were not recorded in this study, such as viral load, may also influence SVR.

– A higher proportion of patients with HCV G2 and G3 achieved an SVR compared with patients with G1.

– Patients with mild-to-moderate levels of fibrosis (F0–F2) achieved higher SVR rates than patients with severe fibrosis/cirrhosis (F3–F4) (which was present in over one third of patients with available histology in this study).

11/14/05

Reference
N Abadir and others. Pegetron prospective optimal weight-based dosing response program (POWeR): preliminary results. Abstract 67524. 56^th annual meeting of the American Association for the Study of Liver Diseases (56^th AASLD). November 11-15, 2005. San Francisco, CA.