Treatment of chronic hepatitis C with consensus interferon

A multicenter, randomized, controlled trial

Myron J. Tong, K. Rajender Reddy, William M. Lee, Paul J. Pockros, John C. Hoefs, Emmet B. Keeffe, F. Blaine Hollinger, E. Jenny Hathcote, Heather White, Robert T. Foust, Donald M. Jensen, Edward L. Krawitt, Hans Fromm, Martin Black, Lawrence M. Blatt, Michael Klein, John Lubina, R. Bailey, K. Bala, L. Balart & 28 others H. Bonkovsky, W. Cassidy, John R. Craig, J. Donovan, Geoffrey M. Dusheiko, M. Ehrinpreis, G. Everson, S. Feinman, S. Hauser, E. Hunter, S. James, P. Killenberg, S. Lee, D. J. Van Leeuwen, H. Lesesne, H. Lieberman, T. Lissoos, L. Lumeng, K. Lyche, G. Minuk, K. Mullen, K. M. Payne, N. Pimstone, J. Poterucha, H. Rosenblate, D. Shafritz, C. Smith, B. Willems

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-α2b). Patients were randomized to receive CIFN at doses of 3 μg or 9 μg, or 15 μg IFN-α2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-μg dose than the 3-μg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-μg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-μg IFN-α2b cohort. However, patients receiving 9 μg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 μg IFN-α2b over the course of treatment (P <.01). Similarly, analysis of patients infected with FICV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-μg CIFN group when compared with the 15-μg IFN-α2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 μg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-μg IFN-α2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 μg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

Original languageEnglish (US)
Pages (from-to)747-754
Number of pages8
JournalHepatology
Volume26
Issue number3
StatePublished - Sep 1997

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interferon alfa-2b
Chronic Hepatitis C
Interferons
Randomized Controlled Trials
Hepacivirus
RNA
Serum
Interferon Type I
Therapeutics
Alanine Transaminase
Genotype
Reverse Transcription
Antibody Formation
Limit of Detection
Anti-Idiotypic Antibodies
Histology
Observation

ASJC Scopus subject areas

  • Hepatology

Cite this

Tong, M. J., Reddy, K. R., Lee, W. M., Pockros, P. J., Hoefs, J. C., Keeffe, E. B., ... Willems, B. (1997). Treatment of chronic hepatitis C with consensus interferon: A multicenter, randomized, controlled trial. Hepatology, 26(3), 747-754.

Treatment of chronic hepatitis C with consensus interferon : A multicenter, randomized, controlled trial. / Tong, Myron J.; Reddy, K. Rajender; Lee, William M.; Pockros, Paul J.; Hoefs, John C.; Keeffe, Emmet B.; Hollinger, F. Blaine; Hathcote, E. Jenny; White, Heather; Foust, Robert T.; Jensen, Donald M.; Krawitt, Edward L.; Fromm, Hans; Black, Martin; Blatt, Lawrence M.; Klein, Michael; Lubina, John; Bailey, R.; Bala, K.; Balart, L.; Bonkovsky, H.; Cassidy, W.; Craig, John R.; Donovan, J.; Dusheiko, Geoffrey M.; Ehrinpreis, M.; Everson, G.; Feinman, S.; Hauser, S.; Hunter, E.; James, S.; Killenberg, P.; Lee, S.; Van Leeuwen, D. J.; Lesesne, H.; Lieberman, H.; Lissoos, T.; Lumeng, L.; Lyche, K.; Minuk, G.; Mullen, K.; Payne, K. M.; Pimstone, N.; Poterucha, J.; Rosenblate, H.; Shafritz, D.; Smith, C.; Willems, B.

In: Hepatology, Vol. 26, No. 3, 09.1997, p. 747-754.

Research output: Contribution to journalArticle

Tong, MJ, Reddy, KR, Lee, WM, Pockros, PJ, Hoefs, JC, Keeffe, EB, Hollinger, FB, Hathcote, EJ, White, H, Foust, RT, Jensen, DM, Krawitt, EL, Fromm, H, Black, M, Blatt, LM, Klein, M, Lubina, J, Bailey, R, Bala, K, Balart, L, Bonkovsky, H, Cassidy, W, Craig, JR, Donovan, J, Dusheiko, GM, Ehrinpreis, M, Everson, G, Feinman, S, Hauser, S, Hunter, E, James, S, Killenberg, P, Lee, S, Van Leeuwen, DJ, Lesesne, H, Lieberman, H, Lissoos, T, Lumeng, L, Lyche, K, Minuk, G, Mullen, K, Payne, KM, Pimstone, N, Poterucha, J, Rosenblate, H, Shafritz, D, Smith, C & Willems, B 1997, 'Treatment of chronic hepatitis C with consensus interferon: A multicenter, randomized, controlled trial', Hepatology, vol. 26, no. 3, pp. 747-754.
Tong MJ, Reddy KR, Lee WM, Pockros PJ, Hoefs JC, Keeffe EB et al. Treatment of chronic hepatitis C with consensus interferon: A multicenter, randomized, controlled trial. Hepatology. 1997 Sep;26(3):747-754.
Tong, Myron J. ; Reddy, K. Rajender ; Lee, William M. ; Pockros, Paul J. ; Hoefs, John C. ; Keeffe, Emmet B. ; Hollinger, F. Blaine ; Hathcote, E. Jenny ; White, Heather ; Foust, Robert T. ; Jensen, Donald M. ; Krawitt, Edward L. ; Fromm, Hans ; Black, Martin ; Blatt, Lawrence M. ; Klein, Michael ; Lubina, John ; Bailey, R. ; Bala, K. ; Balart, L. ; Bonkovsky, H. ; Cassidy, W. ; Craig, John R. ; Donovan, J. ; Dusheiko, Geoffrey M. ; Ehrinpreis, M. ; Everson, G. ; Feinman, S. ; Hauser, S. ; Hunter, E. ; James, S. ; Killenberg, P. ; Lee, S. ; Van Leeuwen, D. J. ; Lesesne, H. ; Lieberman, H. ; Lissoos, T. ; Lumeng, L. ; Lyche, K. ; Minuk, G. ; Mullen, K. ; Payne, K. M. ; Pimstone, N. ; Poterucha, J. ; Rosenblate, H. ; Shafritz, D. ; Smith, C. ; Willems, B. / Treatment of chronic hepatitis C with consensus interferon : A multicenter, randomized, controlled trial. In: Hepatology. 1997 ; Vol. 26, No. 3. pp. 747-754.
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abstract = "This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-α2b). Patients were randomized to receive CIFN at doses of 3 μg or 9 μg, or 15 μg IFN-α2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-μg dose than the 3-μg dose. The sustained ALT and HCV RNA response rates were 20.3{\%} and 12.1{\%}, respectively, in the 9-μg CIFN cohort and 19.6{\%} and 11.3{\%}, respectively, in the 15-μg IFN-α2b cohort. However, patients receiving 9 μg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 μg IFN-α2b over the course of treatment (P <.01). Similarly, analysis of patients infected with FICV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-μg CIFN group when compared with the 15-μg IFN-α2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 μg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-μg IFN-α2b cohort at the end of treatment (24{\%} vs. 15{\%}; P = .04). Improvements in liver histology were noted in all three treatment groups; 52{\%} to 55{\%} of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 μg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.",
author = "Tong, {Myron J.} and Reddy, {K. Rajender} and Lee, {William M.} and Pockros, {Paul J.} and Hoefs, {John C.} and Keeffe, {Emmet B.} and Hollinger, {F. Blaine} and Hathcote, {E. Jenny} and Heather White and Foust, {Robert T.} and Jensen, {Donald M.} and Krawitt, {Edward L.} and Hans Fromm and Martin Black and Blatt, {Lawrence M.} and Michael Klein and John Lubina and R. Bailey and K. Bala and L. Balart and H. Bonkovsky and W. Cassidy and Craig, {John R.} and J. Donovan and Dusheiko, {Geoffrey M.} and M. Ehrinpreis and G. Everson and S. Feinman and S. Hauser and E. Hunter and S. James and P. Killenberg and S. Lee and {Van Leeuwen}, {D. J.} and H. Lesesne and H. Lieberman and T. Lissoos and L. Lumeng and K. Lyche and G. Minuk and K. Mullen and Payne, {K. M.} and N. Pimstone and J. Poterucha and H. Rosenblate and D. Shafritz and C. Smith and B. Willems",
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TY - JOUR

T1 - Treatment of chronic hepatitis C with consensus interferon

T2 - A multicenter, randomized, controlled trial

AU - Tong, Myron J.

AU - Reddy, K. Rajender

AU - Lee, William M.

AU - Pockros, Paul J.

AU - Hoefs, John C.

AU - Keeffe, Emmet B.

AU - Hollinger, F. Blaine

AU - Hathcote, E. Jenny

AU - White, Heather

AU - Foust, Robert T.

AU - Jensen, Donald M.

AU - Krawitt, Edward L.

AU - Fromm, Hans

AU - Black, Martin

AU - Blatt, Lawrence M.

AU - Klein, Michael

AU - Lubina, John

AU - Bailey, R.

AU - Bala, K.

AU - Balart, L.

AU - Bonkovsky, H.

AU - Cassidy, W.

AU - Craig, John R.

AU - Donovan, J.

AU - Dusheiko, Geoffrey M.

AU - Ehrinpreis, M.

AU - Everson, G.

AU - Feinman, S.

AU - Hauser, S.

AU - Hunter, E.

AU - James, S.

AU - Killenberg, P.

AU - Lee, S.

AU - Van Leeuwen, D. J.

AU - Lesesne, H.

AU - Lieberman, H.

AU - Lissoos, T.

AU - Lumeng, L.

AU - Lyche, K.

AU - Minuk, G.

AU - Mullen, K.

AU - Payne, K. M.

AU - Pimstone, N.

AU - Poterucha, J.

AU - Rosenblate, H.

AU - Shafritz, D.

AU - Smith, C.

AU - Willems, B.

PY - 1997/9

Y1 - 1997/9

N2 - This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-α2b). Patients were randomized to receive CIFN at doses of 3 μg or 9 μg, or 15 μg IFN-α2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-μg dose than the 3-μg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-μg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-μg IFN-α2b cohort. However, patients receiving 9 μg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 μg IFN-α2b over the course of treatment (P <.01). Similarly, analysis of patients infected with FICV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-μg CIFN group when compared with the 15-μg IFN-α2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 μg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-μg IFN-α2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 μg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

AB - This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-α2b). Patients were randomized to receive CIFN at doses of 3 μg or 9 μg, or 15 μg IFN-α2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-μg dose than the 3-μg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-μg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-μg IFN-α2b cohort. However, patients receiving 9 μg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 μg IFN-α2b over the course of treatment (P <.01). Similarly, analysis of patients infected with FICV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-μg CIFN group when compared with the 15-μg IFN-α2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 μg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-μg IFN-α2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 μg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

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