Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared withinterferon alpha-2a in noncirrhotic patients with chronic hepatitis C

Administration of interferon (IFN) 3 times weekly in patients with chronic hepatitis C (CHC) is associated with low sustained responses, which may be, in part, related to this regimen's inability to maintain IFN concentration s sufficient to suppress viral replication. An enhanced IFN molecule produc ed by the covalent attachment of a branched 40-kd polyethylene glycol moiet y to IFN alpha -2a (PEG[40kd] IFN alpha -2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with u nmodified IFN alpha -2a. One hundred fifty-nine patients with CHC participa ted in a randomized, ascending-dose (45 or 90, 180, 270 mug) study comparin g PEG(40kd) IFN alpha -2a administered once weekly with 3 MIU IFN alpha -2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN alpha -2a dose for subsequent clinical trials. Efficacy was assessed by measuring hepatitis C virus (HCV) RNA following a 24-week treat ment-free period. Sustained virological responses for PEG(40kd) IFN alpha - 2a once weekly were 10% (45 mug; not significant), 30% (90 mug; P =,009), 3 6% (180 mug; P = .0006), and 29% (270 mug; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN alpha -2a regimen. The types and frequencies o f adverse events and laboratory abnormalities were similar among all groups . In conclusion, once-weekly PEG(40kd) IFN alpha -2a was associated with a higher number of sustained virological responses compared with IFN alpha -2 a 3 times weekly in patients with CHC, but had a similar safety profile. Th e 180-mug PEG(40kd) IFN alpha -2a dose appeared to be the optimal dose base d on sustained virological response and its associated side-effect profile.