Affect of Viral Load on SVR Rates to PegIntron/RBV in Genotype 1 in WIN-R Study

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Affect of Viral Load on SVR Rates to PegIntron/RBV in Genotype 1 in

WIN-R Study

“Stratification of Viral Load in Patients With Genotype 1 HCV:

Impact on Sustained Virologic Response in the WIN-R Trialâ€

Reported by Jules Levin

DDW, May 2006, Los Angeles

ABSTRACT

Background: Pretreatment hepatitis C (HCV) viral levels have been

associated with the likelihood of achieving a sustained virologic

response (SVR) during the course of antiviral therapy with pegylated

interferon and ribavirin (RBV).

Aim: To assess the relationship of pretreatment HCV viral load with

SVR rates in patients with genotype 1 using data from the WIN-R

Trial, the largest HCV therapeutic trial to date.

Methods: Patients in a community setting with chronic hepatitis C

were randomized to Peg IFN alfa-2b 1.5 ug/kg once weekly plus RBV 800

mg/day or RBV based on weight: <65 kg-800 mg/day, 65 to 85 kg-1000

mg/day, >85 to 105 kg-1200 mg/day, and >105-125 kg-1400 mg/day.

Treatment was 48 weeks for patients with HCV genotype 1. Follow-up

for all patients was 24 weeks. HCV RNA was determined by PCR

(Taqman/SPRI) at weeks 24, 48, and 72. SVR rates were analyzed

according to baseline HCV viral loads in patients with genotype 1.

Low viral load at baseline was defined as <2 million copies/ml; high

viral load was defined as >2 million copies/ml.

Results: 225 sites enrolled 4913 patients (2444 FD and 2469 WBD) who

received at least one dose of drug. Intention-to-treat analysis

showed a significant improvement (p=0.04) in SVR with WBD

(1,111/2,469 = 45%)

compared to FD (1,029/2,444 = 42%). 3018 patients had genotype 1 with

an overall SVR rate of 33% (984/3018).

In patients with genotype 1, SVR rates were significantly higher (p =

0.004) in patients with a low HCV viral load (37%, 358/967) than in

those with a high viral load (31%, 532/1739). SVR rates in patients

with viral load <2 million copies/ml were compared with patients with

viral loads >/= 2 million copies/ml.

Reductions in SVR were noted in more patient groups with baseline HCV

RNA levels of 2-15 million copies/ml than in patients with >15

million copies/ml.

Conclusion: Within the genotype 1 patient population with high viral

load as defined traditionally (> 2 million copies/ml), those with

very high viral loads do not have impaired rates of SVR.

Abstract was updated from submitted version.

Background

o Pretreatment hepatitis C virus (HCV) viral load is thought to

influence the likelihood of achieving a sustained virologic response

(SVR) during antiviral therapy with pegylated interferon (PEG-IFN)

and ribavirin (RBV)

o Two million copies/mL has traditionally been considered the cutoff

for high viral load (HVL)

Aim

o To assess the relationship of pretreatment HCV viral load with SVR

rates in patients with HCV genotype 1 using data from the WIN-R

Trial, the largest HCV therapeutic trial to date

Methods

o Patients with chronic hepatitis C in academic and community

settings throughout the United States were randomized to PEG-IFN alfa-

2b (PegIntron®) 1.5 ug/kg/week plus RBV 800 mg/day or RBV based on

weight Treatment was 48 weeks for patients with HCV genotype 1;

follow-up was 24 weeks

o HCV RNA levels were measured with polymerase chain reaction

(Taqman; Schering-Plough Research Institute; lower limit of

detectability was 100 copies/mL, which is equilavant to 29 IU/mL) at

weeks 24, 48, and 72

o This study was designed before adoption of the International Units

system. Therefore, results are reported in copies/mL

o SVR rates were analyzed according to baseline HCV viral loads in

patients with genotype 1

- Low viral load (LVL) was defined as <2 million copies/mL

- HVL was defined as >2 million copies/mL

o A total of 4913 patients were enrolled in the WIN-R trial at 225

sites, received at least 1 dose of drug, and were included in the

primary safety analysis

- A total of 2444 patients were randomized to RBV fixed dosing (FD)

- A total of 2469 patients were randomized to RBV weight-based dosing

(WBD)

RESULTS

Patients

o Of the 4913 patients enrolled in the WIN-R trial, 3018 had HCV

genotype 1 and were included in this analysis

o Mean age was 46 years for the study population; mean weight was

84.3 kg

Primary Efficacy Analysis

o The primary efficacy analysis in the WIN-R trial was SVR rates in

patients weighing >/= 65 kg

o In patients weighing >/= 65 kg with gentotype 1, significantly more

patients in the WBD group achieved SVR than in the FD group -

However, when analyzed by viral load, there was a significant

difference only for those patients in the HVL group (WBD, 32% vs FD,

27%; P = .047)

HVL Versus LVL in Patients With HCV Genotype 1 (All Patients)

Author Summary

o In genotype 1 patients, WBD of ribavirin results in significantly

greater SVR rates than FD

o Among patients with genotype 1 HVL, SVR rates do not appear to

deteriorate with incremental increases in HCV viral load

o In this study, the highest SVR rates occurred in patients with HCV

viral loads of <500,000 copies/mL

Author Conclusions

o Unexpectedly, patients with HCV genotype 1 and HVL do not have

progressively lower SVR as viral load increases

o Very high viral levels in patients with HCV genotype 1 should not

discourage attempts at viral eradication

o Further studies are needed to reevaluate the current cutoff of 2

million copies/mL used to differentiate patients with low and high

HCV viral loads