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

K. R. Reddy, T. L. Wright, P. J. Pockros, M. Shiffman, G. Everson, R. Reindollar, M. W. Fried, P. P. Purdum, D. Jensen, C. Smith, W. M. Lee, T. D. Boyer, A. Lin, S. Pedder, J. DePamphilis

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Abstract

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 α-2a (PEG[40kd] IFN α-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α-2a administered once weekly with 3 MIU IFN α-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α-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 α-2a once weekly were 10% (45 μg; not significant), 30% (90 μg; P = .009), 36% (180 μg; P = .0006), and 29% (270 μg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN α-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN α-2a was associated with a higher number of sustained virological responses compared with IFN α-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-μg PEG(40kd) IFN α-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.

Original languageEnglish (US)
Pages (from-to)433-438
Number of pages6
JournalHepatology
Volume33
Issue number2
DOIs
StatePublished - 2001

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Chronic Hepatitis C
Interferons
Safety
Hepacivirus

ASJC Scopus subject areas

  • Hepatology

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Reddy, K. R., Wright, T. L., Pockros, P. J., Shiffman, M., Everson, G., Reindollar, R., ... DePamphilis, J. (2001). Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in noncirrhotic patients with chronic hepatitis C. Hepatology, 33(2), 433-438. https://doi.org/10.1053/jhep.2001.21747

Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in noncirrhotic patients with chronic hepatitis C. / Reddy, K. R.; Wright, T. L.; Pockros, P. J.; Shiffman, M.; Everson, G.; Reindollar, R.; Fried, M. W.; Purdum, P. P.; Jensen, D.; Smith, C.; Lee, W. M.; Boyer, T. D.; Lin, A.; Pedder, S.; DePamphilis, J.

In: Hepatology, Vol. 33, No. 2, 2001, p. 433-438.

Research output: Contribution to journalArticle

Reddy, KR, Wright, TL, Pockros, PJ, Shiffman, M, Everson, G, Reindollar, R, Fried, MW, Purdum, PP, Jensen, D, Smith, C, Lee, WM, Boyer, TD, Lin, A, Pedder, S & DePamphilis, J 2001, 'Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in noncirrhotic patients with chronic hepatitis C', Hepatology, vol. 33, no. 2, pp. 433-438. https://doi.org/10.1053/jhep.2001.21747
Reddy, K. R. ; Wright, T. L. ; Pockros, P. J. ; Shiffman, M. ; Everson, G. ; Reindollar, R. ; Fried, M. W. ; Purdum, P. P. ; Jensen, D. ; Smith, C. ; Lee, W. M. ; Boyer, T. D. ; Lin, A. ; Pedder, S. ; DePamphilis, J. / Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in noncirrhotic patients with chronic hepatitis C. In: Hepatology. 2001 ; Vol. 33, No. 2. pp. 433-438.
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abstract = "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 α-2a (PEG[40kd] IFN α-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α-2a administered once weekly with 3 MIU IFN α-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α-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 α-2a once weekly were 10{\%} (45 μg; not significant), 30{\%} (90 μg; P = .009), 36{\%} (180 μg; P = .0006), and 29{\%} (270 μg; P = .004), compared with 3{\%} for the 3-times-weekly 3-MIU IFN α-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN α-2a was associated with a higher number of sustained virological responses compared with IFN α-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-μg PEG(40kd) IFN α-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.",
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AU - Reddy, K. R.

AU - Wright, T. L.

AU - Pockros, P. J.

AU - Shiffman, M.

AU - Everson, G.

AU - Reindollar, R.

AU - Fried, M. W.

AU - Purdum, P. P.

AU - Jensen, D.

AU - Smith, C.

AU - Lee, W. M.

AU - Boyer, T. D.

AU - Lin, A.

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AU - DePamphilis, J.

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N2 - 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 α-2a (PEG[40kd] IFN α-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α-2a administered once weekly with 3 MIU IFN α-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α-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 α-2a once weekly were 10% (45 μg; not significant), 30% (90 μg; P = .009), 36% (180 μg; P = .0006), and 29% (270 μg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN α-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN α-2a was associated with a higher number of sustained virological responses compared with IFN α-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-μg PEG(40kd) IFN α-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.

AB - 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 α-2a (PEG[40kd] IFN α-2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α-2a. One hundred fifty-nine patients with CHC participated in a randomized, ascending-dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α-2a administered once weekly with 3 MIU IFN α-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α-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 α-2a once weekly were 10% (45 μg; not significant), 30% (90 μg; P = .009), 36% (180 μg; P = .0006), and 29% (270 μg; P = .004), compared with 3% for the 3-times-weekly 3-MIU IFN α-2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once-weekly PEG(40kd) IFN α-2a was associated with a higher number of sustained virological responses compared with IFN α-2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180-μg PEG(40kd) IFN α-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile.

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