Extended Treatment Duration
Download
1 / 18

Introduction - PowerPoint PPT Presentation


  • 118 Views
  • Uploaded on

Extended Treatment Duration in Chronic Hepatitis C Genotype 1 Infected Slow-Responders: Final Results of the SUCCESS Study. M. Buti, Y. Lurie, N.G. Zakharova, N.P. Blokhina, A. Horban, C. Sarrazin, L. Balciuniene, R. Chen, X. Yu, R. Faruqi, R. Esteban.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Introduction' - knox-scott


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Extended Treatment Duration in Chronic Hepatitis C Genotype 1 Infected Slow-Responders:Final Results of the SUCCESS Study

M. Buti, Y. Lurie, N.G. Zakharova,N.P. Blokhina, A. Horban, C. Sarrazin,L. Balciuniene, R. Chen, X. Yu, R. Faruqi,R. Esteban

44th Annual Meeting of the European Association for the Study of the Liver Sunday April 26, 2009; 12:30-12:45, Hall A2Copenhagen, Denmark


Introduction
Introduction

  • Some studies suggest that extending treatment from 48 to 72 weeks could increase SVR in G1 patients who are slow responders1-3

  • However, definition of slow response varies depending on the study (non-RVR2, partial early virologic response1-3). In addition, the ribavirin dose is suboptimal in many1-2; both factors affect the SVR rate

  • Berg T, et al. Gastroenterology. 2006;130:1086-1097.

  • Sanchez-Tapias JM, et al. Gastroenterology. 2006;131:451-460.

  • Pearlman BL, et al. Hepatology. 2007;46:1688-1694.


Objectives
Objectives

  • Evaluate the efficacy and safety of extended treatment with PEG-IFN alfa-2b plus weight-based RBV in G1 slow responders

    • Slow responders are patients with detectable HCV-RNA with ≥2 log viral reduction at TW 12 and undetectable HCV RNA at TW 24

  • Primary Efficacy End Point

    • SVR for slow responders treated for 48 or 72 weeks

  • Secondary End Points

    • Relapse rate

    • Safety


Study design
Study Design

  • Enrolled 1,428 treatment-naive patients with chronic HCV G1

Week 12

Week 24

Week 72

Week 48

HCV-RNA (+)

and <2 log10 ↓

Stop therapy

Stop therapy

HCV-RNA (+)

PEG-IFN alfa-2b + RBV 12 weeks Tx

PEG-IFN alfa-2b 1.5 µg/kg/wk + RBV 0.8 1.4mg/d 12 weeks Tx

PEG-IFN alfa-2b + RBV :24 weeks Tx

Group A

HCV-RNA (+)

and ≥2 log10

HCV-RNA (-)

Group B

PEG-IFN alfa-2b + RBV:48 weeks Tx

Slow Responders

HCV-RNA (-)

PEG-IFN alfa-2b + RBV :36 weeks Tx

Group C

118 centers in Europe, Canada, Puerto Rico, and Israel participated in this study.


Key inclusion criteria
Key Inclusion Criteria

  • Age 18–70 years

  • Treatment-naive

  • Chronic HCV G1 infection

  • Detectable HCV-RNA

  • Elevated serum ALT levels

  • Liver biopsy (within 18 months) consistent with chronic hepatitis

  • Compensated liver disease


Patient disposition
Patient Disposition

  • Enrolled 1,428 treatment-naive patients with chronic HCV G1

Week 12

Week 24

Week 72

Week 48

HCV-RNA (+)

and <2 log10 ↓

Stop therapy

Nonrespondersn = 444 (31.3%)

Stop therapy

HCV-RNA (+)

PEG-IFN alfa-2b + RBV 12 weeks T

HCV-RNA (+)

and ≥2 log10

Group An = 86

PEG-IFN alfa-2b 1.5 RBV 0.8-1.4mg/d: 12 weeks TxN = 1419

PEG-IFN alfa-2b + RBV 24 weeks Tx

HCV-RNA (-)

Group B n = 73

PEG-IFN alfa-2b + RBV 48 weeks Tx

Slow Responders n=159 (11.2%)

HCV-RNA (-)

PEG-IFN alfa-2b+ RBV 36 weeks Tx

Group Cn = 816 (57.5%)

HCV-RNA Central lab Roche TaqMan assay (LLQ = 30 IU/mL)


Patient demographics
Patient Demographics

SD = standard deviation.


Most slow responders had high baseline viral load
Most Slow Responders Had High Baseline Viral Load



P < .0001

P = .6445

SVR With 72-Week Treatment Was Not Statistically Superior to 48-Week Treatment in Slow Responders (ITT Analysis)

649/816

37/86

35/73

———Slow Responders ———

Complete EVR


P = .6341

SVR Was Not Statistically Different Between 72- and 48-Week Treatment Groups in Slow Responders (Per Protocol Analysis)

37/85

35/72

Slow Responders


SVR was not statistically different between 72-week treatment and 48-week treatment among 80/80/80 Compliance* and Completers†

P = 0.2802

P = 0.1952

n=56

n=79

n=78

n=56

*The subsets of all treated subjects meeting the criteria for fast or slow response and who took at least 80%of the planned dose of each of the study medications (peginterferon and ribavirin) for at least 80% of the assigned treatment duration

†The subsets of all treated population meeting the criteria for fast or slow response and who completed the planned course of treatment as per the Case Report Form Subject Status section


P treatment and 48-week treatment among 80/80/80 Compliance < .0001 37.0%†

P = .1699 14.4%*

Relapse Rates Were Not Statistically Different Between 72- and 48-Week Treatment Groups in Slow Responders

Patients, %

Relapse: 16/49

Relapse: 32/68

Relapse: 71/702

——-Slow Responders ——

Complete EVR

*95% CI: 3.3%, 32.1%.†95% CI: 24.9%, 49.0%.


Logistic regression analysis
Logistic Regression Analysis treatment and 48-week treatment among 80/80/80 Compliance

  • Weight

    • <75 vs >75 kg

  • Age

    • 40–60 vs >60 y

    • <40 vs >60 y

  • Week 12 HCV-RNA

    • 50–5000 vs >5000 IU/mL

    • 50 vs >5000 IU/mL

  • Baseline Viral Load

    • ≤ vs > 800,000 IU/mL

  • Treatment Arm

    • A vs B

      All Analyses NS except for Age <40 vs > 60 y (p = 0.0149)


Rates of adverse events were similar among treatment groups
Rates of Adverse Events Were Similar Among Treatment Groups treatment and 48-week treatment among 80/80/80 Compliance


Summary
Summary treatment and 48-week treatment among 80/80/80 Compliance

  • This, the largest prospective study among naïve G1 slow responders, demonstrated no statistically significant differences in SVR or relapse rates between 48 and 72 weeks of treatment when ribavirin is adjusted according to body weight

  • However there is a numerical trend toward improved SVR and reduced relapse rates for the 72 wks therapy


Summary1
Summary treatment and 48-week treatment among 80/80/80 Compliance

  • No unexpected safety concerns were reported

  • Higher discontinuation rates may be associated with extended treatment period

  • Among Complete EVR patients, 80% achieved SVR similar to those observed in the IDEAL study


Study investigators
Study Investigators treatment and 48-week treatment among 80/80/80 Compliance

Frank H Anderson

Jose D Pedreira Andrade

Joachim C Arnold

Ligita Balciuniene

Simon Bar-Meir

Harry P Bassaris

Manuel Garcia Bengoechea

Thomas Berg

Frieder Berr

Marc Bilodeau

Natalia P Blokhina

Danielle Botta-Fridlund

Marc Bourliere

Peter Buggisch

Mads R Buhl

Patrice Cacoub

Jose Luis Calleja

Andreas Cerny

Janusz Cianciara

Matthew Cramp

Antonio Craxi

Jens Encke

Lajos Dalmi

Jean Delwaide

Dimitrios Dimitroulopoulos

Halyna Dubynska

Martti Farkkila

Saya Victor Feinman

Jon Florholmen

Manuel Rodriguez Garcia

Cornelia Gelbmann

Guido Gerken

Judit Gervain

Andrzej Gietka

Andrzej Gladysz

Tobias Goeser

Olga A Golubovska

Jean-Jacques Gonvers

Michael Gschwantler

Natalya B Gubergrits

Rainer Gunther

Dominique Guyader

Waldemar Halota

Markus H Heim

Vaclav Hejda

Borys A Herasun

Christophe Hezode

Nir Hilzenrat

Andrzej Horban

Dominika Ipatova

Algimantas Irnius

Viktor Jancsik

Jacek Juszczyk

Kelly Kaita

Lars N Karlsen

Natalya V Kharchenko

Hartwig Klinker

John Koskinas

Tomas Krechler

Dominique Larrey

Mark Levstik

Alfredo Juan Lopez-Morante

Yoav Lurie

Spilios Manolakopoulos

Jose Maria

Oscar Nunez Martinez

Rafael Barcena Marugan

Philippe Mathurin

Leopoldo Matos

Stefan Mauss

Ehud Melzer

Larysa V Moroz

Viatcheslav G Morozov

Beat Mullhaupt

Rafael Esteban Mur

Frederik Nevens

Assy Nimer

Blai Dalmau Obrador

Ricardo Moreno Otero

Denis Ouzan

Court Pedersen

Giovambattista Pinzello

Viver Pi-Suner

Vladimir V Rafalsky

Maria Raptopoulou-Gigi

Jens Rasenack

Jose Aguilar Reina

Helmer Ring-Larsen

Mario Rizzetto

Federico Rodriguez-Perez

Jose Such Ronda

Fernando Pons Romero

Siegbert Rossol

Stephen Ryder

Jose Sanchez-Tapias

Rui Sarmento e Castro

Christoph Sarrazin

Jordi Ortiz Seuma

Stephen Shafran

Daniel Shouval

Emanuel Sikuler

Manfred V Singer

Jan Sperl

Zilvinas Sukys

Jolanta Sumskiene

Gerlinde Teuber

Valentyn Topolnytskyy

Albert Tran

Christian Trepo

Petr Urbanek

Jose M Zozaya Urmenata

Ola R Weiland

Johan Westin

Karl H Wiedemann

Florence Wong

Cristina Valente

Jean-Pierre Vinel

Zhanna I Vozianova

Eric Yoshida

Reinhart Zachoval

Natalia G Zakharova

Jean-Pierre Zarski

Eli Zuckerman


ad