Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection

John G. McHutchison, Eric J. Lawitz, Mitchell L. Shiffman, Andrew J. Muir, Greg W. Galler, Jonathan McCone, Lisa M. Nyberg, William M. Lee, Reem H. Ghalib, Eugene R. Schiff, Joseph S. Galati, Bruce R. Bacon, Mitchell N. Davis, Pabak Mukhopadhyay, Kenneth Koury, Stephanie Noviello, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, Mark S. Sulkowski

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Abstract

BACKGROUND: Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. METHODS: At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen. RESULTS: Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose peginterferon alfa-2b; P = 0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], -2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and -1.1% (95% CI, -5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. CONCLUSIONS: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.govnumber, NCT00081770.)

Original languageEnglish (US)
Pages (from-to)580-593
Number of pages14
JournalNew England Journal of Medicine
Volume361
Issue number6
DOIs
StatePublished - Aug 6 2009

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Ribavirin
Hepatitis C
Infection
Hepacivirus
Confidence Intervals
Therapeutics
peginterferon alfa-2b
Genotype
Safety
Chronic Hepatitis C
Virus Diseases
peginterferon alfa-2a

ASJC Scopus subject areas

  • Medicine(all)

Cite this

McHutchison, J. G., Lawitz, E. J., Shiffman, M. L., Muir, A. J., Galler, G. W., McCone, J., ... Sulkowski, M. S. (2009). Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. New England Journal of Medicine, 361(6), 580-593. https://doi.org/10.1056/NEJMoa0808010

Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. / McHutchison, John G.; Lawitz, Eric J.; Shiffman, Mitchell L.; Muir, Andrew J.; Galler, Greg W.; McCone, Jonathan; Nyberg, Lisa M.; Lee, William M.; Ghalib, Reem H.; Schiff, Eugene R.; Galati, Joseph S.; Bacon, Bruce R.; Davis, Mitchell N.; Mukhopadhyay, Pabak; Koury, Kenneth; Noviello, Stephanie; Pedicone, Lisa D.; Brass, Clifford A.; Albrecht, Janice K.; Sulkowski, Mark S.

In: New England Journal of Medicine, Vol. 361, No. 6, 06.08.2009, p. 580-593.

Research output: Contribution to journalArticle

McHutchison, JG, Lawitz, EJ, Shiffman, ML, Muir, AJ, Galler, GW, McCone, J, Nyberg, LM, Lee, WM, Ghalib, RH, Schiff, ER, Galati, JS, Bacon, BR, Davis, MN, Mukhopadhyay, P, Koury, K, Noviello, S, Pedicone, LD, Brass, CA, Albrecht, JK & Sulkowski, MS 2009, 'Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection', New England Journal of Medicine, vol. 361, no. 6, pp. 580-593. https://doi.org/10.1056/NEJMoa0808010
McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. New England Journal of Medicine. 2009 Aug 6;361(6):580-593. https://doi.org/10.1056/NEJMoa0808010
McHutchison, John G. ; Lawitz, Eric J. ; Shiffman, Mitchell L. ; Muir, Andrew J. ; Galler, Greg W. ; McCone, Jonathan ; Nyberg, Lisa M. ; Lee, William M. ; Ghalib, Reem H. ; Schiff, Eugene R. ; Galati, Joseph S. ; Bacon, Bruce R. ; Davis, Mitchell N. ; Mukhopadhyay, Pabak ; Koury, Kenneth ; Noviello, Stephanie ; Pedicone, Lisa D. ; Brass, Clifford A. ; Albrecht, Janice K. ; Sulkowski, Mark S. / Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. In: New England Journal of Medicine. 2009 ; Vol. 361, No. 6. pp. 580-593.
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title = "Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection",
abstract = "BACKGROUND: Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. METHODS: At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen. RESULTS: Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8{\%} with standard-dose peginterferon alfa-2b, 38.0{\%} with low-dose peginterferon alfa-2b, and 40.9{\%} with peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose peginterferon alfa-2b; P = 0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8{\%} (95{\%} confidence interval [CI], -2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and -1.1{\%} (95{\%} CI, -5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5{\%} (95{\%} CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0{\%} (95{\%} CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5{\%} (95{\%} CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7{\%} of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2{\%} and 78.7{\%}, respectively. CONCLUSIONS: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.govnumber, NCT00081770.)",
author = "McHutchison, {John G.} and Lawitz, {Eric J.} and Shiffman, {Mitchell L.} and Muir, {Andrew J.} and Galler, {Greg W.} and Jonathan McCone and Nyberg, {Lisa M.} and Lee, {William M.} and Ghalib, {Reem H.} and Schiff, {Eugene R.} and Galati, {Joseph S.} and Bacon, {Bruce R.} and Davis, {Mitchell N.} and Pabak Mukhopadhyay and Kenneth Koury and Stephanie Noviello and Pedicone, {Lisa D.} and Brass, {Clifford A.} and Albrecht, {Janice K.} and Sulkowski, {Mark S.}",
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TY - JOUR

T1 - Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection

AU - McHutchison, John G.

AU - Lawitz, Eric J.

AU - Shiffman, Mitchell L.

AU - Muir, Andrew J.

AU - Galler, Greg W.

AU - McCone, Jonathan

AU - Nyberg, Lisa M.

AU - Lee, William M.

AU - Ghalib, Reem H.

AU - Schiff, Eugene R.

AU - Galati, Joseph S.

AU - Bacon, Bruce R.

AU - Davis, Mitchell N.

AU - Mukhopadhyay, Pabak

AU - Koury, Kenneth

AU - Noviello, Stephanie

AU - Pedicone, Lisa D.

AU - Brass, Clifford A.

AU - Albrecht, Janice K.

AU - Sulkowski, Mark S.

PY - 2009/8/6

Y1 - 2009/8/6

N2 - BACKGROUND: Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. METHODS: At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen. RESULTS: Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose peginterferon alfa-2b; P = 0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], -2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and -1.1% (95% CI, -5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. CONCLUSIONS: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.govnumber, NCT00081770.)

AB - BACKGROUND: Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. METHODS: At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen. RESULTS: Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P = 0.20 for standarddose vs. low-dose peginterferon alfa-2b; P = 0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], -2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and -1.1% (95% CI, -5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. CONCLUSIONS: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.govnumber, NCT00081770.)

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