Randomized Trial of Peginterferon alfa-2b and
Ribavirin for 48 or 72 Weeks in Patients
with Hepatitis C Virus Genotype 1 and
Slow Virologic Response
Maria Buti,1Yoav Lurie,2Natalia G. Zakharova,3Natalia P. Blokhina,4Andrzej Horban,5
Gerlinde Teuber,6Christoph Sarrazin,6Ligita Balciuniene,7Saya V. Feinman,8Rab Faruqi,9
Lisa D. Pedicone,9and Rafael Esteban1; for the SUCCESS Study Investigators
The benefit of extending treatment duration with peginterferon (PEG-IFN) and ribavirin
(RBV) from 48 weeks to 72 weeks for patients with chronic hepatitis C genotype 1 infec-
tion has not been well established. In this prospective, international, open-label, random-
ized, multicenter study, 1,428 treatment-naı ¨ve patients from 133 centers were treated with
PEG-IFN alfa-2b (1.5 lg/kg/week) plus RBV (800-1,400 mg/day). Patients with detectable
hepatitis C virus (HCV) RNA and a ?2-log10drop in HCV RNA levels at week 12 (slow
responders) were randomized 1:1 to receive 48 weeks (n 5 86) or 72 weeks (n 5 73) of
treatment. Sustained virologic response (SVR) rates were 43% in slow responders treated
for 48 weeks and 48% in slow responders treated for 72 weeks (P 5 0.644). Relapse rates
were similar in slow responders treated for 48 or 72 weeks (47% versus 33%, P 5 0.169).
The safety profile was similar in both treatment arms; serious adverse events leading to dis-
continuation of treatment were observed in 3.5% of slow responders treated for 48 weeks
and 8.2% of those treated for 72 weeks. Among slow responders with a <2-log drop in
HCV RNA at week 8, SVR was 39% in the 72-week arm and 19% in the 48-week arm.
Conclusion: These data suggest that 48 weeks of therapy with PEG-IFN alfa-2b plus RBV
(800-1,400 mg/day) should remain a standard-of-care treatment for treatment-naı ¨ve G1
slow responders. (HEPATOLOGY 2010;52:1201-1207)
(CHC) genotype 1 (G1) infection and achieves sus-
tained virologic response (SVR) in 40%-52% of
treated patients.1-4Because these response rates are
largely unsatisfactory, an individualized approach to
treatment of hepatitis C is increasingly being adopted.
In this approach, total treatment duration is deter-
mined according to the first time during therapy that
hepatitis C virus (HCV) RNA becomes undetectable.
eginterferon (PEG-IFN) alfa-2a or alfa-2b plus
ribavirin (RBV) for 48 weeks is the standard of
care for patients with chronic hepatitis C
The length of time that each patient maintains unde-
tectable HCV RNA while on treatment is directly cor-
related to the likelihood of SVR.4,5
Several studies adopting this approach have shown
that extending therapy to 72 weeks may increase SVR
rates in selected G1 patients.6-11However, the on-treat-
ment virologic criteria used to select patients for
extended therapy vary across studies. Accurately defining
which G1 patients will benefit from extended treatment
is important, because prolonged treatment is associated
with increased adverse events and higher costs.
Abbreviations: cEVR, complete early virologic response; CHC, chronic hepatitis C; CI, confidence interval; G1, genotype 1; HCV, hepatitis C virus; PEG-IFN,
peginterferon; RBV, ribavirin; SVR, sustained virologic response.
From the1Liver Unit, Valle d’Hebron (Ciberehd) University Hospital, and Biomedical Research Center Network in the Area of Hepatic and Digestive Disorders of
the Carlos III Health Institute, Barcelona, Spain; the2Sourasky Medical Center, Tel Aviv, Israel; the3St. Petersburg Municipal Center of Prophylactic AIDS and
Obvodny Channel, St. Petersburg, Russia;4Clinical Infection Hospital #1, Volokolamskoye Shosse, Moscow, Russia; the5Warsaw Medical University & Hospital of
Infectious Diseases, Warsaw, Poland;6J.W. Goethe University Hospital, Frankfurt, Germany; the7Vilnius University Hospital of Tuberculosis and Infection Diseases,
Santarisˇke ˙s, Lithuania;8Mount Sinai Hospital, Toronto, Ontario, Canada; and9Schering-Plough Corporation, Whitehouse Station, NJ.
Received April 30, 2010; accepted June 10, 2010.
Supported by Schering-Plough Corporation (currently Merck & Co., Inc.).
Address reprint requests to: Dr. Maria Buti, Paseo Valle de Hebron 119-129, Servicio de Hepatologi, Hospital Vall d’Hebro ´n and CIBERehd del Instituto
Carlos III, Barcelona, Spain 08036. E-mail: firstname.lastname@example.org; fax: (34)-934274495.
RNA drop by week 4, a further 60% attain a similar
response between weeks 4 and 8, and the remaining
20% attain this response between weeks 8 and 12. Pre-
dictive analyses suggest that absence of a 2-log drop in
HCV RNA level at week 8 warrants prospective evalu-
ation as a criterion for identifying patients who may
be suitable for extended treatment duration. Approxi-
mately 80% of all slow responders had a ?2-log drop
in viremia at week 8, and ?50% of these attained an
SVR, irrespective of treatment duration (there was no
benefit associated with extending treatment duration in
this cohort). In contrast, ?20% of slow responders failed
to attain a ?2-log drop at week 8; among this cohort,
SVR rates were 19% with 48 weeks of treatment and
39% with 72 weeks of treatment. Although based on
small patient numbers (and excluding those with body
weight >125 kg), these data indicate that patients with a
<2-log decline at week 8 and undetectable HCV RNA
at week 24 represent the group of patients who will ben-
efit most from extended treatment.
In conclusion, SVR rates were similar among slow
responders who received a standard dose of PEG-IFN
alfa-2b and weight-based RBV for 48 or 72 weeks.
Thus, current practice and recommendations regarding
prolonged therapy in slow responders are not sup-
ported by the results of our study and consequently
require re-evaluation. The adverse event profiles were
also similar; however, the rates of discontinuation were
higher for the 72-week regimen. A 48-week regimen
of PEG-IFN alfa-2b and RBV should remain a stand-
ard of care for these patients.
by T. Ibbotson, Ph.D., and C. Knight, Pharm.D.
The SUCCESS study investigators: F. Berr, M.
Gschwantler (Austria); J. Delwaide, F. Nevens (Belgium);
F. Anderson, M. Bilodeau, S. Feinman, N. Hilzenrat,
K. Kaita, M. Levstik, S. Shafran, F. Wong, E. Yoshida
(Canada); V. Hejda, T. Krechler, J. Sperl, P. Urbanek
(Czech Republic); M. Buhl, C. Pedersen, H. Ring-
Larsen (Denmark); M. Farkkila (Finland); D. Botta-
Fridlundg, M. Bourliere, P. Cacoub, D. Guyader, C.
Hezode, D. Larrey, P. Mathurin, D. Ouzan, A. Tran,
C. Trepo, J.-P. Vinel, J.-P. Zarski (France); J. Arnold,
T. Berg, P. Buggisch, J. Encke, C. Gelbmann, G.
Gerken, T. Goeser, R. Gunther, H. Klinker, S. Mauss,
J. Rasenack, S. Rossol, M. Singer, G. Teuber, K.
Wiedmann, R. Zachoval (Germany); H. Bassaris, D.
Dimitroulopoulos, J. Koskinas, S. Manolakopoulos,
M. Raptopoulou-Gigi (Greece); L. Dalmi, J. Gervain,
V. Jancsik (Hungary); S. Bar-Meir, E. Melzer, A.
Nimer, D. Shouval, E. Sikuler, E. Zuckerman (Israel);
A. Craxi, G. Pinzello, M. Rizzetto (Italy); A. Irnius, Z.
Writing assistance was provided
Sukys, J. Sumskiene (Lithuania); J. Florholmen, L.
Karlsen (Norway); J. Cianciara, A. Gietka, A. Gladysz,
W. Halota, J. Juszczyk (Poland); L. Matos, R. Sar-
mento e Castro, C. Valente (Portugal); F. Rodriguez-
Perez (Puerto Rico); V. Morozov, V. Rafalsky (Russia);
J. Aguilar Reina, R. Barcena Marugan, J. Calleja, B.
Dalmau Obrador, M. Garcia Bengoechea, A. Lopez
Morante, R. Moreno Otero, O. Nunez Martinez, J.
Ortiz Seuma, J. Pedreira Andrade, F. Pons Romero, M.
Rodriguez Garcia, J. Sanchez-Tapias, J. Such Ronda,
J. Viver Pi-Suner, J. Zozaya Urmenata (Spain); O.
Weiland, J. Westin (Sweden); A. Cerny, J.-J. Gonvers,
M. Heim, B. Mullhaupt (Switzerland); H. Dubynska,
O. Golubovska, N. Gubergrits, B. Herasun, D. Ipatova,
N. Kharchenko, L. Moroz, V. Topolnytskyy, Z. Vozia-
nova (Ukraine); M. Cramp, S. Ryder (United Kingdom).
1. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M,
Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with
interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis
C: a randomised trial. Lancet 2001;358:958-965.
2. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales
FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C
virus infection. N Engl J Med 2002;347:975-982.
3. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin
P, et al. Peginterferon-a2a and ribavirin combination therapy in chronic
hepatitis C: a randomized study of treatment duration and ribavirin
dose. Ann Intern Med 2004;140:346-355.
4. 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. N Engl J Med 2009;361:580-593.
5. Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta
V, et al. Individualized treatment duration for hepatitis C genotype 1
patients: a randomized controlled trial. HEPATOLOGY 2008;47:
6. Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T,
et al. Extended treatment duration for hepatitis C virus type 1:
comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin.
7. Sanchez-Tapias JM, Diago M, Escartin P, Enriquez J, Romero-Gomez
M, Barcena R, et al. Peginterferon-alfa2a plus ribavirin for 48 versus
72 weeks in patients with detectable hepatitis C virus RNA at week 4
of treatment. Gastroenterology 2006;131:451-460.
8. Buti M, Valdes A, Sanchez-Avila F, Esteban R, Lurie Y. Extending com-
bination therapy with peginterferon alfa-2b plus ribavirin for genotype
1 chronic hepatitis C late responders: a report of 9 cases. HEPATOLOGY
9. Brouwer JT, Nevens F, Bekkering FC, Bourgeois N, Van Vlierberghe
H, Weegink CJ, et al. Reduction of relapse rates by 18-month treat-
ment in chronic hepatitis C. A Benelux randomized trial in 300
patients. J Hepatol 2004;40:689-695.
10. Ferenci P, Laferl H, Scherzer TM, Maieron A, Hofer H, Stauber R,
et al. Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C
type 1 and 4 patients with slow virological response. Gastroenterology
11. Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of
peginterferon and ribavirin in hepatitis C genotype 1-infected slow res-
ponders. HEPATOLOGY 2007;46:1688-1694.
12. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, manage-
ment, and treatment of hepatitis C: an update. HEPATOLOGY 2009;49:
HEPATOLOGY, Vol. 52, No. 4, 2010 BUTI ET AL. 1207