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 DiesNeil 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 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

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252 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Jacobson, I. M., Brown, R. S., Freilich, B., Afdhal, N., Kwo, P. Y., Santoro, J., Becker, S., Wakil, A. E., Pound, D., Godofsky, E., Strauss, R., Bernstein, D., Flamm, S., Pauly, M. P., Mukhopadhyay, P., Griffel, L. H., Brass, C. A., Black, M., Fried, M., ... 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