Higher SVR Rates for Patients With Advanced Fibrosis/Cirrhosis Infected With Genotype 2 vs Genotype 3 HCV Following Treatment With Peginterferon alfa-2a and Ribavirin

Posting Date: November 05, 2008

• Retrospective analysis of 2 phase III studies^[1]

Summary of Key Conclusions

• Among HCV-infected patients with advanced fibrosis/cirrhosis, treatment with peginterferon alfa-2a plus ribavirin resulted in higher sustained virologic response (SVR) rates with genotype 2 vs genotype 3 infection
  • For genotype 2 infection, achievement of rapid virologic response (RVR) better predictor of SVR than treatment duration (24 vs 16 weeks)
  • For genotype 3, longer treatment duration and RVR both predictors of SVR
• Shortened (16-week) treatment regimen with advanced fibrosis/cirrhosis only appropriate for genotype 2 HCV–infected patients with low baseline HCV RNA and RVR

Background

• Standard therapy for genotype 2 or 3 chronic HCV infection peginterferon alfa-2a plus ribavirin for 24 weeks^[2]
  • Some studies suggest differences in SVR rates between genotype 2 vs genotype 3 HCV^[3,4]
• Shortened 16-week treatment course effective for genotype 2 or 3 patients with low baseline HCV RNA who achieve RVR^[3]
  • Not known if shorter treatment duration effective with advanced fibrosis/cirrhosis
• Current study assessed effect of genotype (2 vs 3) on SVR in patients with advanced fibrosis/cirrhosis receiving peginterferon alfa-2a plus ribavirin for 16 or 24 weeks

Summary of Study Design

• Retrospective analysis included patients with HCV genotype 2 or genotype 3 infection with advanced fibrosis/cirrhosis at baseline who received peginterferon alfa-2a 180 µg/week plus ribavirin 800 mg/day for 16 or 24 weeks
  • Advanced fibrosis or cirrhosis defined as
    • METAVIR 3-4 or
    • Knodell 3-4 or
    • Ishak 4-6
• Outcomes and parameters
  • RVR: HCV RNA < 50 IU/mL at week 4
  • Complete early virologic response (cEVR): HCV RNA ≥ 50 IU/mL at Week 4 but < 50 IU/mL at Week 12
  • Partial early virologic response: HCV RNA ≥ 50 IU/mL at Weeks 4 and 12 but ≥ 2 log₁₀ decrease from baseline at Week 12
  • End of treatment response: HCV RNA < 50 IU/mL at end of treatment (16 or 24 weeks)
  • SVR: HCV RNA < 50 IU/mL at 24 weeks posttreatment
  • Relapse: no SVR after end of treatment achieved
  • Low baseline HCV RNA: < 400,000 IU/mL
  • High baseline HCV RNA: ≥ 400,000 IU/mL
• Factors associated with SVR identified by multiple logistic regression analyses
  • Baseline factors incorporated: sex, age, race, weight, body mass index, HCV RNA, ALT, ALT-ratio, creatinine clearance, albumin, platelets, neutrophils
  • On-treatment factors incorporated: assigned duration, RVR, ribavirin plus peginterferon alfa-2a dose (cumulative)

Baseline Characteristics

• N = 380
• Genotype 2 patients older with higher levels of HCV RNA vs genotype 3 patients
  • Groups well balanced for other characteristics

Characteristic	Genotype 2 HCV Peginterferon + Ribavirin		Genotype 3 HCV Peginterferon + Ribavirin
	16 Weeks (n = 107)	24 Weeks (n = 99)	16 Weeks (n = 84)	24 Weeks (n = 90)
Male, %	62	68	66	76
Mean age, yrs	52.8	51.8	46.9	45.4
Mean ALT, IU/L	101.7	108.3	106.5	107.1
Mean HCV RNA, IU/mL x 106	5.79	6.27	4.67	4.56

Main Findings

• Overall 24-week treatment regimen associated with higher SVR rates and lower relapse rates across both genotypes
  • Genotype 3 associated with lower SVR and higher relapse rates vs genotype 2

Outcome, %	Genotype 2 HCV Peginterferon + Ribavirin		Genotype 3 HCV Peginterferon + Ribavirin
	16 Weeks (n = 107)	24 Weeks (n = 99)	16 Weeks (n = 84)	24 Weeks (n = 90)
SVR	51	66	44	53
Relapse	45	26	50	34

• Analysis of SVR according to on-treatment factors showed higher rates with RVR vs cEVR across both genotypes receiving 24 weeks of treatment
  • Among genotype 2 patients with RVR, similar SVR rates with 16 and 24 weeks of treatment
  • Among genotype 3 patients with RVR, higher rates of SVR with longer treatment duration

SVR, %	Genotype 2 HCV Peginterferon + Ribavirin		Genotype 3 HCV Peginterferon + Ribavirin
	16 Weeks	24 Weeks	16 Weeks