Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients

A Randomized Trial

Ira M. Jacobson, Robert S. Brown, Bradley Freilich, Nezam Afdhal, Paul Y. Kwo, John Santoro, Scott Becker, Adil E. Wakil, David Pound, Eliot Godofsky, Robert Strauss, David Bernstein, Steven Flamm, Mary Pat Pauly, Pabak Mukhopadhyay, Louis H. Griffel, Clifford A. Brass, Martin Black, Michael Fried, David Dies & 210 others Neil Brodsky, Maurice Cerulli, Stephen Esposito, Michael Rahmin, Jonathan David, Edward Lebovics, Raymond Kenny, Hulya Levendoglu, Lisa Ozick, Peter Gardner, David Berman, David Feldman, Hillel Tobias, Frank Klion, Albert Min, James Ehrlich, Julie Spivack, David Stein, Paul Kwo, Vance VanDrake, Kevin Behrle, John Serini, Howard Monsour, B. Anand, Greg Galler, Rise Stribling, Stephen Kelly, Natarjan Bala, Thomas McDonald, Martha Ghosh, Fredric Gordon, Alain Ades, Myron Brand, Jeffery Cooley, Alan Epstein, Thomas Sepe, George Abraham, R. Agrawal, Mordechai Rabinovitz, Mark Smith, Fred Kilby, David Nunes, James Srour, Seth Richter, Lawton Shick, Peter Varunok, Geoffrey Zucker, Joseph Polito, Micheal Lyons, David Maccini, Geronimo Sahagun, Charles Bedard, Donald Wadland, Fredrich Loura, Arnold Levin, Terry Box, Naoky Tsai, Keith Tolman, Walid Baddoura, Micheal David Bernstein, Joseph DePasquale, Paul Bermanski, David Gabbazaideh, Gerond Lake-Bakaar, Jay Cowan, Curt Hagendom, Alan Fixelle, Raymond Rubin, Clive Albert, Brian Hudes, Mark Murphy, J. Lynn Cochran, Jorge Herrera, Norman Gitlin, Robert Reindollar, Jeffrey Fenyves, Kevin Dye, Thomas Noble, Larry Weprin, Michael Epstein, Robert Finkel, Natarajan Ravendhran, Michael Cox, Rudra Rai, Lou Gelrud, Ira Lobis, Michael Ryan, Vinod Rustgi, Mitchell Shiffman, James Lewis, Jonathan McCone, William Kaplan, David Hurwich, Donna Goldman, Rockford Yapp, Helen Te, Rodger Perez, Allan Weston, Fredric Regenstein, Ronald Rinker, Michael Dragutsky, Barry Migicovsky, Robert Herring, William Ross, William Lyles, Andrew Nelson, Simon Cofrancesco, John King, Thomas Allen, Raj Bhandari, Stuart Gordon, Firdous Siddiqui, Craig Peine, John Gross, John Lake, John Kichner, Jose Franco, James Nelson, James Levin, Samuel Ho, Coleman Smith, Douglas Levin, Michael Henry, Douglas Dalke, Jonathon Jensen, Lawrence Kim, Robert Levine, John Goff, Douglas Brouillette, Stephen J. Lanspa, Robert Manning, Stephen Harrison, Kenneth Diamond, Mitchell Davis, Thuan Nguyen, Rvikumar Vemuru, James Cox, K. Ganeshappa, Harry Matossian, Edward Galen, Pierre Nader, K. Rajender Reddy, Gary Matusow, Steve Carlson, Jean Luc Szpakowski, Karl Esrason, Thai Van Pham, Alexander Lee, Timothy Jenkins, Joanna Ready, Nathan Kam, Lyle Shlager, Neville Pimstone, Ramsey Cheung, Helen Wong, Thomas Hargrave, Diana Sylvestre, Kenneth Devault, Avanish Aggarwal, Darrell Schwertner, Timothy Cavacini, Terence Reisman, Louis Lambiase, Donate Ricci, Mark Eisner, S. Lawrence Rothman, Michael Bloom, Arthur Berman, Paul Yudelman, Scott Wiesen, Murali Shankar, Thomas Rosenfield, John Vierling, David Schulman, Steven Huy Han, Kip Lyche, Franco Felizarta, Lino Deguzman, Donald Hillebrand, Bonnie Bock, Trong Nguyen Tuan, Michael Demicco, Graham Woolf, Victor Araya, Ellen Shaw, Lawrence Stein, K. Digregorio, Carl D'Angelo, James Thornton, Steve Chen, John Jolley, Norah Terrault, Robert Gish, Ronald Wasserman, Thomas Layden, David Van Thiel, Donald Jensen, Mark Levstik, Ronald Pruitt, Gerald Siciliano, Bennett Cecil, Luis Marsano, Mark Jonas, Whit Knapple, Vijay Balan, Daniel Meline, Steven Palley, Leon Rigberg, David Winston, Tarek Hassanein

Research output: Contribution to journalArticle

250 Citations (Scopus)

Abstract

This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 μmg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. Conclusion: PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

Original languageEnglish
Pages (from-to)971-981
Number of pages11
JournalHepatology
Volume46
Issue number4
DOIs
StatePublished - Oct 2007

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Ribavirin
Chronic Hepatitis C
Weights and Measures
Genotype
Safety
peginterferon alfa-2b
Intention to Treat Analysis
Therapeutics
Viral Load
Hepacivirus
Weight Loss
Hemoglobins
Research Personnel
RNA

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Jacobson, I. M., Brown, R. S., Freilich, B., Afdhal, N., Kwo, P. Y., Santoro, J., ... Hassanein, T. (2007). Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial. Hepatology, 46(4), 971-981. https://doi.org/10.1002/hep.21932

Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients : A Randomized Trial. / Jacobson, Ira M.; Brown, Robert S.; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul Y.; Santoro, John; Becker, Scott; Wakil, Adil E.; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauly, Mary Pat; Mukhopadhyay, Pabak; Griffel, Louis H.; Brass, Clifford A.; Black, Martin; Fried, Michael; Dies, David; Brodsky, Neil; Cerulli, Maurice; Esposito, Stephen; Rahmin, Michael; David, Jonathan; Lebovics, Edward; Kenny, Raymond; Levendoglu, Hulya; Ozick, Lisa; Gardner, Peter; Berman, David; Feldman, David; Tobias, Hillel; Klion, Frank; Min, Albert; Ehrlich, James; Spivack, Julie; Stein, David; Kwo, Paul; VanDrake, Vance; Behrle, Kevin; Serini, John; Monsour, Howard; Anand, B.; Galler, Greg; Stribling, Rise; Kelly, Stephen; Bala, Natarjan; McDonald, Thomas; Ghosh, Martha; Gordon, Fredric; Ades, Alain; Brand, Myron; Cooley, Jeffery; Epstein, Alan; Sepe, Thomas; Abraham, George; Agrawal, R.; Rabinovitz, Mordechai; Smith, Mark; Kilby, Fred; Nunes, David; Srour, James; Richter, Seth; Shick, Lawton; Varunok, Peter; Zucker, Geoffrey; Polito, Joseph; Lyons, Micheal; Maccini, David; Sahagun, Geronimo; Bedard, Charles; Wadland, Donald; Loura, Fredrich; Levin, Arnold; Box, Terry; Tsai, Naoky; Tolman, Keith; Baddoura, Walid; Bernstein, Micheal David; DePasquale, Joseph; Bermanski, Paul; Gabbazaideh, David; Lake-Bakaar, Gerond; Cowan, Jay; Hagendom, Curt; Fixelle, Alan; Rubin, Raymond; Albert, Clive; Hudes, Brian; Murphy, Mark; Cochran, J. Lynn; Herrera, Jorge; Gitlin, Norman; Reindollar, Robert; Fenyves, Jeffrey; Dye, Kevin; Noble, Thomas; Weprin, Larry; Epstein, Michael; Finkel, Robert; Ravendhran, Natarajan; Cox, Michael; Rai, Rudra; Gelrud, Lou; Lobis, Ira; Ryan, Michael; Rustgi, Vinod; Shiffman, Mitchell; Lewis, James; McCone, Jonathan; Kaplan, William; Hurwich, David; Goldman, Donna; Yapp, Rockford; Te, Helen; Perez, Rodger; Weston, Allan; Regenstein, Fredric; Rinker, Ronald; Dragutsky, Michael; Migicovsky, Barry; Herring, Robert; Ross, William; Lyles, William; Nelson, Andrew; Cofrancesco, Simon; King, John; Allen, Thomas; Bhandari, Raj; Gordon, Stuart; Siddiqui, Firdous; Peine, Craig; Gross, John; Lake, John; Kichner, John; Franco, Jose; Nelson, James; Levin, James; Ho, Samuel; Smith, Coleman; Levin, Douglas; Henry, Michael; Dalke, Douglas; Jensen, Jonathon; Kim, Lawrence; Levine, Robert; Goff, John; Brouillette, Douglas; Lanspa, Stephen J.; Manning, Robert; Harrison, Stephen; Diamond, Kenneth; Davis, Mitchell; Nguyen, Thuan; Vemuru, Rvikumar; Cox, James; Ganeshappa, K.; Matossian, Harry; Galen, Edward; Nader, Pierre; Reddy, K. Rajender; Matusow, Gary; Carlson, Steve; Szpakowski, Jean Luc; Esrason, Karl; Pham, Thai Van; Lee, Alexander; Jenkins, Timothy; Ready, Joanna; Kam, Nathan; Shlager, Lyle; Pimstone, Neville; Cheung, Ramsey; Wong, Helen; Hargrave, Thomas; Sylvestre, Diana; Devault, Kenneth; Aggarwal, Avanish; Schwertner, Darrell; Cavacini, Timothy; Reisman, Terence; Lambiase, Louis; Ricci, Donate; Eisner, Mark; Rothman, S. Lawrence; Bloom, Michael; Berman, Arthur; Yudelman, Paul; Wiesen, Scott; Shankar, Murali; Rosenfield, Thomas; Vierling, John; Schulman, David; Han, Steven Huy; Lyche, Kip; Felizarta, Franco; Deguzman, Lino; Hillebrand, Donald; Bock, Bonnie; Tuan, Trong Nguyen; Demicco, Michael; Woolf, Graham; Araya, Victor; Shaw, Ellen; Stein, Lawrence; Digregorio, K.; D'Angelo, Carl; Thornton, James; Chen, Steve; Jolley, John; Terrault, Norah; Gish, Robert; Wasserman, Ronald; Layden, Thomas; Van Thiel, David; Jensen, Donald; Levstik, Mark; Pruitt, Ronald; Siciliano, Gerald; Cecil, Bennett; Marsano, Luis; Jonas, Mark; Knapple, Whit; Balan, Vijay; Meline, Daniel; Palley, Steven; Rigberg, Leon; Winston, David; Hassanein, Tarek.

In: Hepatology, Vol. 46, No. 4, 10.2007, p. 971-981.

Research output: Contribution to journalArticle

Jacobson, IM, Brown, RS, Freilich, B, Afdhal, N, Kwo, PY, Santoro, J, Becker, S, Wakil, AE, Pound, D, Godofsky, E, Strauss, R, Bernstein, D, Flamm, S, Pauly, MP, Mukhopadhyay, P, Griffel, LH, Brass, CA, Black, M, Fried, M, Dies, D, Brodsky, N, Cerulli, M, Esposito, S, Rahmin, M, David, J, Lebovics, E, Kenny, R, Levendoglu, H, Ozick, L, Gardner, P, Berman, D, Feldman, D, Tobias, H, Klion, F, Min, A, Ehrlich, J, Spivack, J, Stein, D, Kwo, P, VanDrake, V, Behrle, K, Serini, J, Monsour, H, Anand, B, Galler, G, Stribling, R, Kelly, S, Bala, N, McDonald, T, Ghosh, M, Gordon, F, Ades, A, Brand, M, Cooley, J, Epstein, A, Sepe, T, Abraham, G, Agrawal, R, Rabinovitz, M, Smith, M, Kilby, F, Nunes, D, Srour, J, Richter, S, Shick, L, Varunok, P, Zucker, G, Polito, J, Lyons, M, Maccini, D, Sahagun, G, Bedard, C, Wadland, D, Loura, F, Levin, A, Box, T, Tsai, N, Tolman, K, Baddoura, W, Bernstein, MD, DePasquale, J, Bermanski, P, Gabbazaideh, D, Lake-Bakaar, G, Cowan, J, Hagendom, C, Fixelle, A, Rubin, R, Albert, C, Hudes, B, Murphy, M, Cochran, JL, Herrera, J, Gitlin, N, Reindollar, R, Fenyves, J, Dye, K, Noble, T, Weprin, L, Epstein, M, Finkel, R, Ravendhran, N, Cox, M, Rai, R, Gelrud, L, Lobis, I, Ryan, M, Rustgi, V, Shiffman, M, Lewis, J, McCone, J, Kaplan, W, Hurwich, D, Goldman, D, Yapp, R, Te, H, Perez, R, Weston, A, Regenstein, F, Rinker, R, Dragutsky, M, Migicovsky, B, Herring, R, Ross, W, Lyles, W, Nelson, A, Cofrancesco, S, King, J, Allen, T, Bhandari, R, Gordon, S, Siddiqui, F, Peine, C, Gross, J, Lake, J, Kichner, J, Franco, J, Nelson, J, Levin, J, Ho, S, Smith, C, Levin, D, Henry, M, Dalke, D, Jensen, J, Kim, L, Levine, R, Goff, J, Brouillette, D, Lanspa, SJ, Manning, R, Harrison, S, Diamond, K, Davis, M, Nguyen, T, Vemuru, R, Cox, J, Ganeshappa, K, Matossian, H, Galen, E, Nader, P, Reddy, KR, Matusow, G, Carlson, S, Szpakowski, JL, Esrason, K, Pham, TV, Lee, A, Jenkins, T, Ready, J, Kam, N, Shlager, L, Pimstone, N, Cheung, R, Wong, H, Hargrave, T, Sylvestre, D, Devault, K, Aggarwal, A, Schwertner, D, Cavacini, T, Reisman, T, Lambiase, L, Ricci, D, Eisner, M, Rothman, SL, Bloom, M, Berman, A, Yudelman, P, Wiesen, S, Shankar, M, Rosenfield, T, Vierling, J, Schulman, D, Han, SH, Lyche, K, Felizarta, F, Deguzman, L, Hillebrand, D, Bock, B, Tuan, TN, Demicco, M, Woolf, G, Araya, V, Shaw, E, Stein, L, Digregorio, K, D'Angelo, C, Thornton, J, Chen, S, Jolley, J, Terrault, N, Gish, R, Wasserman, R, Layden, T, Van Thiel, D, Jensen, D, Levstik, M, Pruitt, R, Siciliano, G, Cecil, B, Marsano, L, Jonas, M, Knapple, W, Balan, V, Meline, D, Palley, S, Rigberg, L, Winston, D & Hassanein, T 2007, 'Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial', Hepatology, vol. 46, no. 4, pp. 971-981. https://doi.org/10.1002/hep.21932
Jacobson, Ira M. ; Brown, Robert S. ; Freilich, Bradley ; Afdhal, Nezam ; Kwo, Paul Y. ; Santoro, John ; Becker, Scott ; Wakil, Adil E. ; Pound, David ; Godofsky, Eliot ; Strauss, Robert ; Bernstein, David ; Flamm, Steven ; Pauly, Mary Pat ; Mukhopadhyay, Pabak ; Griffel, Louis H. ; Brass, Clifford A. ; Black, Martin ; Fried, Michael ; Dies, David ; Brodsky, Neil ; Cerulli, Maurice ; Esposito, Stephen ; Rahmin, Michael ; David, Jonathan ; Lebovics, Edward ; Kenny, Raymond ; Levendoglu, Hulya ; Ozick, Lisa ; Gardner, Peter ; Berman, David ; Feldman, David ; Tobias, Hillel ; Klion, Frank ; Min, Albert ; Ehrlich, James ; Spivack, Julie ; Stein, David ; Kwo, Paul ; VanDrake, Vance ; Behrle, Kevin ; Serini, John ; Monsour, Howard ; Anand, B. ; Galler, Greg ; Stribling, Rise ; Kelly, Stephen ; Bala, Natarjan ; McDonald, Thomas ; Ghosh, Martha ; Gordon, Fredric ; Ades, Alain ; Brand, Myron ; Cooley, Jeffery ; Epstein, Alan ; Sepe, Thomas ; Abraham, George ; Agrawal, R. ; Rabinovitz, Mordechai ; Smith, Mark ; Kilby, Fred ; Nunes, David ; Srour, James ; Richter, Seth ; Shick, Lawton ; Varunok, Peter ; Zucker, Geoffrey ; Polito, Joseph ; Lyons, Micheal ; Maccini, David ; Sahagun, Geronimo ; Bedard, Charles ; Wadland, Donald ; Loura, Fredrich ; Levin, Arnold ; Box, Terry ; Tsai, Naoky ; Tolman, Keith ; Baddoura, Walid ; Bernstein, Micheal David ; DePasquale, Joseph ; Bermanski, Paul ; Gabbazaideh, David ; Lake-Bakaar, Gerond ; Cowan, Jay ; Hagendom, Curt ; Fixelle, Alan ; Rubin, Raymond ; Albert, Clive ; Hudes, Brian ; Murphy, Mark ; Cochran, J. Lynn ; Herrera, Jorge ; Gitlin, Norman ; Reindollar, Robert ; Fenyves, Jeffrey ; Dye, Kevin ; Noble, Thomas ; Weprin, Larry ; Epstein, Michael ; Finkel, Robert ; Ravendhran, Natarajan ; Cox, Michael ; Rai, Rudra ; Gelrud, Lou ; Lobis, Ira ; Ryan, Michael ; Rustgi, Vinod ; Shiffman, Mitchell ; Lewis, James ; McCone, Jonathan ; Kaplan, William ; Hurwich, David ; Goldman, Donna ; Yapp, Rockford ; Te, Helen ; Perez, Rodger ; Weston, Allan ; Regenstein, Fredric ; Rinker, Ronald ; Dragutsky, Michael ; Migicovsky, Barry ; Herring, Robert ; Ross, William ; Lyles, William ; Nelson, Andrew ; Cofrancesco, Simon ; King, John ; Allen, Thomas ; Bhandari, Raj ; Gordon, Stuart ; Siddiqui, Firdous ; Peine, Craig ; Gross, John ; Lake, John ; Kichner, John ; Franco, Jose ; Nelson, James ; Levin, James ; Ho, Samuel ; Smith, Coleman ; Levin, Douglas ; Henry, Michael ; Dalke, Douglas ; Jensen, Jonathon ; Kim, Lawrence ; Levine, Robert ; Goff, John ; Brouillette, Douglas ; Lanspa, Stephen J. ; Manning, Robert ; Harrison, Stephen ; Diamond, Kenneth ; Davis, Mitchell ; Nguyen, Thuan ; Vemuru, Rvikumar ; Cox, James ; Ganeshappa, K. ; Matossian, Harry ; Galen, Edward ; Nader, Pierre ; Reddy, K. Rajender ; Matusow, Gary ; Carlson, Steve ; Szpakowski, Jean Luc ; Esrason, Karl ; Pham, Thai Van ; Lee, Alexander ; Jenkins, Timothy ; Ready, Joanna ; Kam, Nathan ; Shlager, Lyle ; Pimstone, Neville ; Cheung, Ramsey ; Wong, Helen ; Hargrave, Thomas ; Sylvestre, Diana ; Devault, Kenneth ; Aggarwal, Avanish ; Schwertner, Darrell ; Cavacini, Timothy ; Reisman, Terence ; Lambiase, Louis ; Ricci, Donate ; Eisner, Mark ; Rothman, S. Lawrence ; Bloom, Michael ; Berman, Arthur ; Yudelman, Paul ; Wiesen, Scott ; Shankar, Murali ; Rosenfield, Thomas ; Vierling, John ; Schulman, David ; Han, Steven Huy ; Lyche, Kip ; Felizarta, Franco ; Deguzman, Lino ; Hillebrand, Donald ; Bock, Bonnie ; Tuan, Trong Nguyen ; Demicco, Michael ; Woolf, Graham ; Araya, Victor ; Shaw, Ellen ; Stein, Lawrence ; Digregorio, K. ; D'Angelo, Carl ; Thornton, James ; Chen, Steve ; Jolley, John ; Terrault, Norah ; Gish, Robert ; Wasserman, Ronald ; Layden, Thomas ; Van Thiel, David ; Jensen, Donald ; Levstik, Mark ; Pruitt, Ronald ; Siciliano, Gerald ; Cecil, Bennett ; Marsano, Luis ; Jonas, Mark ; Knapple, Whit ; Balan, Vijay ; Meline, Daniel ; Palley, Steven ; Rigberg, Leon ; Winston, David ; Hassanein, Tarek. / Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients : A Randomized Trial. In: Hepatology. 2007 ; Vol. 46, No. 4. pp. 971-981.
@article{346a60e947754830be6a58f42a6241bd,
title = "Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial",
abstract = "This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 μmg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2{\%} versus 40.5{\%}; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0{\%} and 28.9{\%}, respectively, in genotype 1 patients (P = 0.005) and 31.2{\%} and 26.7{\%}, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8{\%} and 59.5{\%}, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. Conclusion: PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.",
author = "Jacobson, {Ira M.} and Brown, {Robert S.} and Bradley Freilich and Nezam Afdhal and Kwo, {Paul Y.} and John Santoro and Scott Becker and Wakil, {Adil E.} and David Pound and Eliot Godofsky and Robert Strauss and David Bernstein and Steven Flamm and Pauly, {Mary Pat} and Pabak Mukhopadhyay and Griffel, {Louis H.} and Brass, {Clifford A.} and Martin Black and Michael Fried and David Dies and Neil Brodsky and Maurice Cerulli and Stephen Esposito and Michael Rahmin and Jonathan David and Edward Lebovics and Raymond Kenny and Hulya Levendoglu and Lisa Ozick and Peter Gardner and David Berman and David Feldman and Hillel Tobias and Frank Klion and Albert Min and James Ehrlich and Julie Spivack and David Stein and Paul Kwo and Vance VanDrake and Kevin Behrle and John Serini and Howard Monsour and B. Anand and Greg Galler and Rise Stribling and Stephen Kelly and Natarjan Bala and Thomas McDonald and Martha Ghosh and Fredric Gordon and Alain Ades and Myron Brand and Jeffery Cooley and Alan Epstein and Thomas Sepe and George Abraham and R. Agrawal and Mordechai Rabinovitz and Mark Smith and Fred Kilby and David Nunes and James Srour and Seth Richter and Lawton Shick and Peter Varunok and Geoffrey Zucker and Joseph Polito and Micheal Lyons and David Maccini and Geronimo Sahagun and Charles Bedard and Donald Wadland and Fredrich Loura and Arnold Levin and Terry Box and Naoky Tsai and Keith Tolman and Walid Baddoura and Bernstein, {Micheal David} and Joseph DePasquale and Paul Bermanski and David Gabbazaideh and Gerond Lake-Bakaar and Jay Cowan and Curt Hagendom and Alan Fixelle and Raymond Rubin and Clive Albert and Brian Hudes and Mark Murphy and Cochran, {J. Lynn} and Jorge Herrera and Norman Gitlin and Robert Reindollar and Jeffrey Fenyves and Kevin Dye and Thomas Noble and Larry Weprin and Michael Epstein and Robert Finkel and Natarajan Ravendhran and Michael Cox and Rudra Rai and Lou Gelrud and Ira Lobis and Michael Ryan and Vinod Rustgi and Mitchell Shiffman and James Lewis and Jonathan McCone and William Kaplan and David Hurwich and Donna Goldman and Rockford Yapp and Helen Te and Rodger Perez and Allan Weston and Fredric Regenstein and Ronald Rinker and Michael Dragutsky and Barry Migicovsky and Robert Herring and William Ross and William Lyles and Andrew Nelson and Simon Cofrancesco and John King and Thomas Allen and Raj Bhandari and Stuart Gordon and Firdous Siddiqui and Craig Peine and John Gross and John Lake and John Kichner and Jose Franco and James Nelson and James Levin and Samuel Ho and Coleman Smith and Douglas Levin and Michael Henry and Douglas Dalke and Jonathon Jensen and Lawrence Kim and Robert Levine and John Goff and Douglas Brouillette and Lanspa, {Stephen J.} and Robert Manning and Stephen Harrison and Kenneth Diamond and Mitchell Davis and Thuan Nguyen and Rvikumar Vemuru and James Cox and K. Ganeshappa and Harry Matossian and Edward Galen and Pierre Nader and Reddy, {K. Rajender} and Gary Matusow and Steve Carlson and Szpakowski, {Jean Luc} and Karl Esrason and Pham, {Thai Van} and Alexander Lee and Timothy Jenkins and Joanna Ready and Nathan Kam and Lyle Shlager and Neville Pimstone and Ramsey Cheung and Helen Wong and Thomas Hargrave and Diana Sylvestre and Kenneth Devault and Avanish Aggarwal and Darrell Schwertner and Timothy Cavacini and Terence Reisman and Louis Lambiase and Donate Ricci and Mark Eisner and Rothman, {S. Lawrence} and Michael Bloom and Arthur Berman and Paul Yudelman and Scott Wiesen and Murali Shankar and Thomas Rosenfield and John Vierling and David Schulman and Han, {Steven Huy} and Kip Lyche and Franco Felizarta and Lino Deguzman and Donald Hillebrand and Bonnie Bock and Tuan, {Trong Nguyen} and Michael Demicco and Graham Woolf and Victor Araya and Ellen Shaw and Lawrence Stein and K. Digregorio and Carl D'Angelo and James Thornton and Steve Chen and John Jolley and Norah Terrault and Robert Gish and Ronald Wasserman and Thomas Layden and {Van Thiel}, David and Donald Jensen and Mark Levstik and Ronald Pruitt and Gerald Siciliano and Bennett Cecil and Luis Marsano and Mark Jonas and Whit Knapple and Vijay Balan and Daniel Meline and Steven Palley and Leon Rigberg and David Winston and Tarek Hassanein",
year = "2007",
month = "10",
doi = "10.1002/hep.21932",
language = "English",
volume = "46",
pages = "971--981",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients

T2 - A Randomized Trial

AU - Jacobson, Ira M.

AU - Brown, Robert S.

AU - Freilich, Bradley

AU - Afdhal, Nezam

AU - Kwo, Paul Y.

AU - Santoro, John

AU - Becker, Scott

AU - Wakil, Adil E.

AU - Pound, David

AU - Godofsky, Eliot

AU - Strauss, Robert

AU - Bernstein, David

AU - Flamm, Steven

AU - Pauly, Mary Pat

AU - Mukhopadhyay, Pabak

AU - Griffel, Louis H.

AU - Brass, Clifford A.

AU - Black, Martin

AU - Fried, Michael

AU - Dies, David

AU - Brodsky, Neil

AU - Cerulli, Maurice

AU - Esposito, Stephen

AU - Rahmin, Michael

AU - David, Jonathan

AU - Lebovics, Edward

AU - Kenny, Raymond

AU - Levendoglu, Hulya

AU - Ozick, Lisa

AU - Gardner, Peter

AU - Berman, David

AU - Feldman, David

AU - Tobias, Hillel

AU - Klion, Frank

AU - Min, Albert

AU - Ehrlich, James

AU - Spivack, Julie

AU - Stein, David

AU - Kwo, Paul

AU - VanDrake, Vance

AU - Behrle, Kevin

AU - Serini, John

AU - Monsour, Howard

AU - Anand, B.

AU - Galler, Greg

AU - Stribling, Rise

AU - Kelly, Stephen

AU - Bala, Natarjan

AU - McDonald, Thomas

AU - Ghosh, Martha

AU - Gordon, Fredric

AU - Ades, Alain

AU - Brand, Myron

AU - Cooley, Jeffery

AU - Epstein, Alan

AU - Sepe, Thomas

AU - Abraham, George

AU - Agrawal, R.

AU - Rabinovitz, Mordechai

AU - Smith, Mark

AU - Kilby, Fred

AU - Nunes, David

AU - Srour, James

AU - Richter, Seth

AU - Shick, Lawton

AU - Varunok, Peter

AU - Zucker, Geoffrey

AU - Polito, Joseph

AU - Lyons, Micheal

AU - Maccini, David

AU - Sahagun, Geronimo

AU - Bedard, Charles

AU - Wadland, Donald

AU - Loura, Fredrich

AU - Levin, Arnold

AU - Box, Terry

AU - Tsai, Naoky

AU - Tolman, Keith

AU - Baddoura, Walid

AU - Bernstein, Micheal David

AU - DePasquale, Joseph

AU - Bermanski, Paul

AU - Gabbazaideh, David

AU - Lake-Bakaar, Gerond

AU - Cowan, Jay

AU - Hagendom, Curt

AU - Fixelle, Alan

AU - Rubin, Raymond

AU - Albert, Clive

AU - Hudes, Brian

AU - Murphy, Mark

AU - Cochran, J. Lynn

AU - Herrera, Jorge

AU - Gitlin, Norman

AU - Reindollar, Robert

AU - Fenyves, Jeffrey

AU - Dye, Kevin

AU - Noble, Thomas

AU - Weprin, Larry

AU - Epstein, Michael

AU - Finkel, Robert

AU - Ravendhran, Natarajan

AU - Cox, Michael

AU - Rai, Rudra

AU - Gelrud, Lou

AU - Lobis, Ira

AU - Ryan, Michael

AU - Rustgi, Vinod

AU - Shiffman, Mitchell

AU - Lewis, James

AU - McCone, Jonathan

AU - Kaplan, William

AU - Hurwich, David

AU - Goldman, Donna

AU - Yapp, Rockford

AU - Te, Helen

AU - Perez, Rodger

AU - Weston, Allan

AU - Regenstein, Fredric

AU - Rinker, Ronald

AU - Dragutsky, Michael

AU - Migicovsky, Barry

AU - Herring, Robert

AU - Ross, William

AU - Lyles, William

AU - Nelson, Andrew

AU - Cofrancesco, Simon

AU - King, John

AU - Allen, Thomas

AU - Bhandari, Raj

AU - Gordon, Stuart

AU - Siddiqui, Firdous

AU - Peine, Craig

AU - Gross, John

AU - Lake, John

AU - Kichner, John

AU - Franco, Jose

AU - Nelson, James

AU - Levin, James

AU - Ho, Samuel

AU - Smith, Coleman

AU - Levin, Douglas

AU - Henry, Michael

AU - Dalke, Douglas

AU - Jensen, Jonathon

AU - Kim, Lawrence

AU - Levine, Robert

AU - Goff, John

AU - Brouillette, Douglas

AU - Lanspa, Stephen J.

AU - Manning, Robert

AU - Harrison, Stephen

AU - Diamond, Kenneth

AU - Davis, Mitchell

AU - Nguyen, Thuan

AU - Vemuru, Rvikumar

AU - Cox, James

AU - Ganeshappa, K.

AU - Matossian, Harry

AU - Galen, Edward

AU - Nader, Pierre

AU - Reddy, K. Rajender

AU - Matusow, Gary

AU - Carlson, Steve

AU - Szpakowski, Jean Luc

AU - Esrason, Karl

AU - Pham, Thai Van

AU - Lee, Alexander

AU - Jenkins, Timothy

AU - Ready, Joanna

AU - Kam, Nathan

AU - Shlager, Lyle

AU - Pimstone, Neville

AU - Cheung, Ramsey

AU - Wong, Helen

AU - Hargrave, Thomas

AU - Sylvestre, Diana

AU - Devault, Kenneth

AU - Aggarwal, Avanish

AU - Schwertner, Darrell

AU - Cavacini, Timothy

AU - Reisman, Terence

AU - Lambiase, Louis

AU - Ricci, Donate

AU - Eisner, Mark

AU - Rothman, S. Lawrence

AU - Bloom, Michael

AU - Berman, Arthur

AU - Yudelman, Paul

AU - Wiesen, Scott

AU - Shankar, Murali

AU - Rosenfield, Thomas

AU - Vierling, John

AU - Schulman, David

AU - Han, Steven Huy

AU - Lyche, Kip

AU - Felizarta, Franco

AU - Deguzman, Lino

AU - Hillebrand, Donald

AU - Bock, Bonnie

AU - Tuan, Trong Nguyen

AU - Demicco, Michael

AU - Woolf, Graham

AU - Araya, Victor

AU - Shaw, Ellen

AU - Stein, Lawrence

AU - Digregorio, K.

AU - D'Angelo, Carl

AU - Thornton, James

AU - Chen, Steve

AU - Jolley, John

AU - Terrault, Norah

AU - Gish, Robert

AU - Wasserman, Ronald

AU - Layden, Thomas

AU - Van Thiel, David

AU - Jensen, Donald

AU - Levstik, Mark

AU - Pruitt, Ronald

AU - Siciliano, Gerald

AU - Cecil, Bennett

AU - Marsano, Luis

AU - Jonas, Mark

AU - Knapple, Whit

AU - Balan, Vijay

AU - Meline, Daniel

AU - Palley, Steven

AU - Rigberg, Leon

AU - Winston, David

AU - Hassanein, Tarek

PY - 2007/10

Y1 - 2007/10

N2 - This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 μmg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. Conclusion: PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

AB - This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 μmg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. Conclusion: PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

UR - http://www.scopus.com/inward/record.url?scp=36348981708&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348981708&partnerID=8YFLogxK

U2 - 10.1002/hep.21932

DO - 10.1002/hep.21932

M3 - Article

VL - 46

SP - 971

EP - 981

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -