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

Author(s): Reddy KR, Wright TL, Pockros PJ, Shiffman M, Everson G, et al.


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 concentrations sufficient to suppress viral replication. An enhanced IFN molecule produced by the covalent attachment of a branched 40-kd polyethylene glycol moiety to IFN alpha-2a (PEG[40kd] IFN alpha-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN alpha-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 microg) study comparing 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 treatment-free period. Sustained virological responses for PEG(40kd) IFN alpha-2a once weekly were 10% (45 microg; not significant), 30% (90 microg; P = .009), 36% (180 microg; P = .0006), and 29% (270 microg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN alpha-2a regimen. The types and frequencies of 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-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-microg PEG(40kd) IFN alpha-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.

Similar Articles

Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome

Author(s): Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, et al.

Global burden of disease (GBD) for hepatitis C

Author(s): Global Burden Of Hepatitis C Working Group

The hepatitis C virus life cycle as a target for new antiviral therapies

Author(s): Pawlotsky JM, Chevaliez S, McHutchison JG

Global distribution and prevalence of hepatitis C virus genotypes

Author(s): Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, et al.

HCV genotypes among 1013 Saudi nationals: a multicenter study

Author(s): Al Traif I, Al Balwi MA, Abdulkarim I, Handoo FA, Alqhamdi HS, et al.

Genetic epidemiology of hepatitis C virus throughout egypt

Author(s): Ray SC, Arthur RR, Carella A, Bukh J, Thomas DL

Telaprevir activity in treatment-naive patients infected hepatitis C virus genotype 4: a randomized trial

Author(s): Benhamou Y, Moussalli J, Ratziu V, Lebray P, De Backer K, et al.

Socioeconomic status in HCV infected patients - risk and prognosis

Author(s): Omland LH, Osler M, Jepsen P, Krarup H, Weis N, et al.

Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4

Author(s): Hasan F, Asker H, Al-Khaldi J, Siddique I, Al-Ajmi M, et al.

Response to pegylated interferon alfa-2a and ribavirin in chronic hepatitis C genotype 4

Author(s): El Makhzangy H, Esmat G, Said M, Elraziky M, Shouman S, et al.

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4

Author(s): Martín-Carbonero L, Puoti M, García-Samaniego J, De Luca A, Losada E, et al.

Sofosbuvir for previously untreated chronic hepatitis C infection

Author(s): Lawitz E, Mangia A Wyles D, Rodriguez-Torres M, Hassanein T, et al.

Efficacy and safety of sofosbuvir-based triple therapy in hepatitis C genotype 4 infection

Author(s): Wehmeyer MH, Jordan S, Lüth S, Hartl J, Stoehr A, et al.

Daclatasvir plus peginterferonalfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study

Author(s): Hézode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, et al.

Daclatasvir and asunaprevir plus peginterferonalfa and ribavirin in HCV genotype 1 or 4 non-responders

Author(s): Jensen D, Sherman KE, Hézode C, Pol S, Zeuzem S, et al.

Hepatitis C virus treatment in the real world: optimising treatment and access to therapies

Author(s): Zoulim F, Liang TJ, Gerbes AL Aghemo A4, Deuffic-Burban S5, et al.

Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4

Author(s): Doss W, Shiha G, Hassany M, Soliman R, Fouad R, et al.

Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection

Author(s): Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, et al.

Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection

Author(s): Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, et al.