Induction Therapy With High-Dose Peginterferon alfa-2b Does Not Improve SVR Rates in Treatment-Naive Patients With Genotype 1 HCV Infection

Posting Date: November 07, 2008

• Prospective, open-label, multicenter, randomized trial^[1]

Summary of Key Conclusions

• No improvement in early virologic response (EVR) or sustained virologic response (SVR) rates in patients infected with genotype 1 HCV receiving high-dose induction therapy with peginterferon alfa-2b vs no high-dose induction
• High-dose induction therapy with peginterferon alfa-2b associated with trend toward higher response rates in heavier patients

Background

• Weekly peginterferon alfa-2b plus weight-based ribavirin standard care for patients infected with HCV
  • SVR rates 42% to 46% (genotype 1) vs 76% to 82% (other genotypes)^[2]
• Treatment strategies to improve SVR rates in genotype 1 HCV-infected patients needed
• Interferon alfa-2b produces biphasic virologic response; first-phase, dose-dependent HCV RNA decline within 24 hours followed by slower, second-phase, dose-independent decline^[3,4]
  • Ribavirin works synergistically with interferon to decrease HCV RNA during second phase
  • High-dose interferon induction therapy may increase first-phase response and enhance SVR rates
• Current study compared standard peginterferon alfa-2b/ribavirin regimen with high-dose peginterferon alfa-2b/ribavirin induction regimen in treatment-naive patients infected with genotype 1 and 4 HCV

Schematic of Study Design

Eligibility

• Genotype 1 and 4 HCV infection
• HCV treatment naive

Baseline Characteristics

• N = 610
• Baseline characteristics well matched between groups with the exception of more patients in induction arm having baseline HCV RNA levels ≥ 800,000 IU/mL
• Predominantly genotype 1 HCV
• Most patients with mild to moderate fibrosis (grade 0-2)

Characteristic	High-Dose Peginterferon alfa-2b Induction (n = 299)	No Induction (n = 311)
Male, %	49.7	50.3
Mean age, yrs ± SD	45 ± 8.4	45 ± 8.9
Race, %
White	68.0	72.3
Latino	13.4	11.6
Black	12.4	12.0
Asian	6.4	4.2
Mean body weight, kg ± SD	84.5 ± 18.7	84.9 ± 17.4
Body weight ≥ 85 kg, %	50.2	52.0
HCV genotype, %
1	98.7	99.0
4	1.3	1.0
Mean HCV RNA level, 106 IU/mL ± SD	6.8 ± 19.3	5.3 ± 13.8
HCV RNA ≥ 800,000 IU/mL,* %	70.9	61.9
Liver fibrosis score
0–2	74.2	76.8
3–4	25.8	23.2
Mean ALT, IU/mL ± SD	93.5 ± 62.9	97.2 ± 105.1

*P = .02

Description of Current Analysis

• Patients from 46 academic and community centers
• Primary endpoint
  • SVR: undetectable HCV RNA 24 weeks after end of treatment (EOT)
  • All treated analysis, missing or withdrawal equals failure

Main Findings

• SVR rates similar between arms (P = .434)

Undetectable HCV RNA (< 50 IU/mL), % (n)	High-Dose Peginterferon alfa-2b Induction (n = 299)	No Induction (n = 310)
Week 12 (EVR)	62 (184)	58 (179)
Week 24	56 (168)	56 (173)
Week 48 (EOT)	42 (126)	39 (121)
SVR (24 weeks EOT)	32 (96)	29 (92)

• No improvement in SVR in black patients with induction therapy (P = .89)
• Trend toward improved SVR with induction therapy in heavier patients (38% with induction vs 28% without; P = .08)

	Undetectable HCV RNA (< 50 IU/mL) by Subgroups
Characteristic, %	Week 12 (EVR)