Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: A randomized trial

被引:220
作者
Jacobson, Ira M.
Brown, Robert S., Jr.
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.
机构
[1] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Ctr Study Hepatitis C, New York, NY USA
[2] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, New York, NY 10032 USA
[3] Baptist Med Ctr, Kansas City, MO USA
[4] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[5] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA
[6] Atlantic Gastroenterol Associates, Egg Harbor Township, NJ USA
[7] Austin Gastroenterol PA, Austin, TX USA
[8] Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco, CA 94115 USA
[9] Indianapolis Gastroenterol RSCH, Indianapolis, IN USA
[10] Bach & Godofsky, Bradenton, FL USA
[11] NW Georgia Gastroenterol Associates PC, Marietta, GA USA
[12] N Shore Univ Hosp, Manhasset, NY USA
[13] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA
[14] Kaiser Permanente, Sacramento, CA USA
[15] Schering Plough Res Inst, Kenilworth, NJ USA
关键词
D O I
10.1002/hep.21932
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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-26 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 mu g/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 I 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.
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收藏
页码:971 / 981
页数:11
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