U.S. multicenter pilot study of daily consensus interferon (CIFN) plus ribavirin for "difficult-to-treat" HCV genotype 1 patients

Abstract

Background: Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection.

Methods: Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3-4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B, n = 31).

Results: Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8-12 weeks, and late virologic response from 16-24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients.

Conclusion: Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.

Fig. 1

Study design and patient outcome

Fig. 2

Patient outcomes. a Percentage of patients with negative hepatitis C virus polymerase chain reaction (HCV PCR) results over time for total cohort and patients in groups A and B. Results include HCV quantitative PCR negative (week 4–20) and HCV qualitative PCR negative (week 24, end of treatment [week 52+]) and end of follow up (week 72+) data. Note: patients who were HCV PCR negative but subsequently dropped out were considered as treatment failures from the time of drop out. b Sustained virologic response (SVR) analysis by study arm and overall SVR result for total cohort. Intention to treat (ITT) and overall per protocol SVR rates

Fig. 3

Patient outcomes by study site. Sites with greater than eight patients enrolled were compared (sites A–D), and other study sites with lower enrollment were grouped together (other low enrollment sites). AA African American

Fig. 4

Dose reductions. a Number and reasons for incidences of consensus interferon (CIFN) dose reduction. b Number and reasons for incidences of ribavirin (RBV) dose reduction

Fig. 5

Number and reasons for incidences of treatment discontinuation