Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

Gregory J Dore; Eric Lawitz; Christophe Hézode; Stephen D Shafran; Alnoor Ramji; Harvey A Tatum; Gloria Taliani; Albert Tran; Maurizia R Brunetto; Serena Zaltron; Simone I Strasser; Nina Weis; Wayne Ghesquiere; Samuel S Lee; Dominique Larrey; Stanislas Pol; Hugh Harley; Jacob George; Scott K Fung; Victor de Lédinghen; Peggy Hagens; Fiona McPhee; Dennis Hernandez; David Cohen; Elizabeth Cooney; Stephanie Noviello; Eric A Hughes

doi:10.1053/j.gastro.2014.10.007

Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

Gregory J Dore, Eric Lawitz, Christophe Hézode, Stephen D Shafran, Alnoor Ramji, Harvey A Tatum, Gloria Taliani, Albert Tran, Maurizia R Brunetto, Serena Zaltron, Simone I Strasser, Nina Weis, Wayne Ghesquiere, Samuel S Lee, Dominique Larrey, Stanislas Pol, Hugh Harley, Jacob George, Scott K Fung, Victor de LédinghenPeggy Hagens, Fiona McPhee, Dennis Hernandez, David Cohen, Elizabeth Cooney, Stephanie Noviello, Eric A Hughes

Institut for Klinisk Medicin

43 Citationer (Scopus)

Abstract

BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy.

METHODS: Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24).

RESULTS: Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy.

CONCLUSIONS: Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.

Originalsprog	Engelsk
Tidsskrift	Gastroenterology
Vol/bind	148
Udgave nummer	2
Sider (fra-til)	355-366.e1
Antal sider	13
ISSN	0016-5085
DOI	https://doi.org/10.1053/j.gastro.2014.10.007
Status	Udgivet - 1 feb. 2015

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10.1053/j.gastro.2014.10.007

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Dore, G. J., Lawitz, E., Hézode, C., Shafran, S. D., Ramji, A., Tatum, H. A., Taliani, G., Tran, A., Brunetto, M. R., Zaltron, S., Strasser, S. I., Weis, N., Ghesquiere, W., Lee, S. S., Larrey, D., Pol, S., Harley, H., George, J., Fung, S. K., ... Hughes, E. A. (2015). Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection. Gastroenterology, 148(2), 355-366.e1. https://doi.org/10.1053/j.gastro.2014.10.007

Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection. / Dore, Gregory J; Lawitz, Eric; Hézode, Christophe et al.
I: Gastroenterology, Bind 148, Nr. 2, 01.02.2015, s. 355-366.e1.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Dore, GJ, Lawitz, E, Hézode, C, Shafran, SD, Ramji, A, Tatum, HA, Taliani, G, Tran, A, Brunetto, MR, Zaltron, S, Strasser, SI, Weis, N, Ghesquiere, W, Lee, SS, Larrey, D, Pol, S, Harley, H, George, J, Fung, SK, de Lédinghen, V, Hagens, P, McPhee, F, Hernandez, D, Cohen, D, Cooney, E, Noviello, S & Hughes, EA 2015, 'Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection', Gastroenterology, bind 148, nr. 2, s. 355-366.e1. https://doi.org/10.1053/j.gastro.2014.10.007

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title = "Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection",

abstract = "BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy.METHODS: Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24).RESULTS: Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy.CONCLUSIONS: Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.",

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author = "Dore, {Gregory J} and Eric Lawitz and Christophe H{\'e}zode and Shafran, {Stephen D} and Alnoor Ramji and Tatum, {Harvey A} and Gloria Taliani and Albert Tran and Brunetto, {Maurizia R} and Serena Zaltron and Strasser, {Simone I} and Nina Weis and Wayne Ghesquiere and Lee, {Samuel S} and Dominique Larrey and Stanislas Pol and Hugh Harley and Jacob George and Fung, {Scott K} and {de L{\'e}dinghen}, Victor and Peggy Hagens and Fiona McPhee and Dennis Hernandez and David Cohen and Elizabeth Cooney and Stephanie Noviello and Hughes, {Eric A}",

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doi = "10.1053/j.gastro.2014.10.007",

language = "English",

volume = "148",

pages = "355--366.e1",

journal = "Gastroenterology",

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TY - JOUR

T1 - Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

AU - Dore, Gregory J

AU - Lawitz, Eric

AU - Hézode, Christophe

AU - Shafran, Stephen D

AU - Ramji, Alnoor

AU - Tatum, Harvey A

AU - Taliani, Gloria

AU - Tran, Albert

AU - Brunetto, Maurizia R

AU - Zaltron, Serena

AU - Strasser, Simone I

AU - Weis, Nina

AU - Ghesquiere, Wayne

AU - Lee, Samuel S

AU - Larrey, Dominique

AU - Pol, Stanislas

AU - Harley, Hugh

AU - George, Jacob

AU - Fung, Scott K

AU - de Lédinghen, Victor

AU - Hagens, Peggy

AU - McPhee, Fiona

AU - Hernandez, Dennis

AU - Cohen, David

AU - Cooney, Elizabeth

AU - Noviello, Stephanie

AU - Hughes, Eric A

PY - 2015/2/1

Y1 - 2015/2/1

N2 - BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy.METHODS: Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24).RESULTS: Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy.CONCLUSIONS: Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.

AB - BACKGROUND & AIMS: Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy.METHODS: Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24).RESULTS: Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy.CONCLUSIONS: Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antiviral Agents

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Genotype

KW - Hepacivirus

KW - Hepatitis C, Chronic

KW - Humans

KW - Imidazoles

KW - Interferon-alpha

KW - Male

KW - Middle Aged

KW - Polyethylene Glycols

KW - RNA, Viral

KW - Recombinant Proteins

KW - Ribavirin

U2 - 10.1053/j.gastro.2014.10.007

DO - 10.1053/j.gastro.2014.10.007

M3 - Journal article

C2 - 25311593

SN - 0016-5085

VL - 148

SP - 355-366.e1

JO - Gastroenterology

JF - Gastroenterology

IS - 2

ER -

Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection

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