Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis

Jia-Horng Kao, Donald M Jensen, Michael P Manns, Ira Jacobson, Hiromitsu Kumada, Joji Toyota, Jeong Heo, Boris Yoffe, William Sievert, Fernando Bessone, Cheng-Yuan Peng, Stuart K Roberts, Youn-Jae Lee, Rafia Bhore, Patricia Mendez, Eric Hughes, Stephanie Noviello

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background Aims: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV). Methods: Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes. Results: In the Japanese phase 3 study, SVR12 was achieved by 91 of patients with cirrhosis (n = 22) and 84 of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84 of patients with cirrhosis (n = 206) and by 85 of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5–4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation. Conclusions: The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.
Original languageEnglish
Pages (from-to)954-962
Number of pages9
JournalLiver International
Volume36
Issue number7
DOIs
Publication statusPublished - 2016

Keywords

  • cirrhosis
  • direct acting antiviral
  • hepatitis C
  • safety

Cite this

Kao, J-H., Jensen, D. M., Manns, M. P., Jacobson, I., Kumada, H., Toyota, J., ... Noviello, S. (2016). Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis. Liver International, 36(7), 954-962. https://doi.org/10.1111/liv.13049
Kao, Jia-Horng ; Jensen, Donald M ; Manns, Michael P ; Jacobson, Ira ; Kumada, Hiromitsu ; Toyota, Joji ; Heo, Jeong ; Yoffe, Boris ; Sievert, William ; Bessone, Fernando ; Peng, Cheng-Yuan ; Roberts, Stuart K ; Lee, Youn-Jae ; Bhore, Rafia ; Mendez, Patricia ; Hughes, Eric ; Noviello, Stephanie. / Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis. In: Liver International. 2016 ; Vol. 36, No. 7. pp. 954-962.
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title = "Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis",
abstract = "Background Aims: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV). Methods: Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes. Results: In the Japanese phase 3 study, SVR12 was achieved by 91 of patients with cirrhosis (n = 22) and 84 of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84 of patients with cirrhosis (n = 206) and by 85 of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10{\%}) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2{\%}, respectively) compared with those without cirrhosis (both 0.6{\%}). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8{\%}) compared with those without cirrhosis (3.5–4.7{\%}). Alanine aminotransferase elevations were not associated with hepatic decompensation. Conclusions: The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.",
keywords = "cirrhosis, direct acting antiviral, hepatitis C, safety",
author = "Jia-Horng Kao and Jensen, {Donald M} and Manns, {Michael P} and Ira Jacobson and Hiromitsu Kumada and Joji Toyota and Jeong Heo and Boris Yoffe and William Sievert and Fernando Bessone and Cheng-Yuan Peng and Roberts, {Stuart K} and Youn-Jae Lee and Rafia Bhore and Patricia Mendez and Eric Hughes and Stephanie Noviello",
year = "2016",
doi = "10.1111/liv.13049",
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Kao, J-H, Jensen, DM, Manns, MP, Jacobson, I, Kumada, H, Toyota, J, Heo, J, Yoffe, B, Sievert, W, Bessone, F, Peng, C-Y, Roberts, SK, Lee, Y-J, Bhore, R, Mendez, P, Hughes, E & Noviello, S 2016, 'Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis' Liver International, vol. 36, no. 7, pp. 954-962. https://doi.org/10.1111/liv.13049

Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis. / Kao, Jia-Horng; Jensen, Donald M; Manns, Michael P; Jacobson, Ira; Kumada, Hiromitsu; Toyota, Joji; Heo, Jeong; Yoffe, Boris; Sievert, William; Bessone, Fernando; Peng, Cheng-Yuan; Roberts, Stuart K; Lee, Youn-Jae; Bhore, Rafia; Mendez, Patricia; Hughes, Eric; Noviello, Stephanie.

In: Liver International, Vol. 36, No. 7, 2016, p. 954-962.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: A pooled analysis

AU - Kao, Jia-Horng

AU - Jensen, Donald M

AU - Manns, Michael P

AU - Jacobson, Ira

AU - Kumada, Hiromitsu

AU - Toyota, Joji

AU - Heo, Jeong

AU - Yoffe, Boris

AU - Sievert, William

AU - Bessone, Fernando

AU - Peng, Cheng-Yuan

AU - Roberts, Stuart K

AU - Lee, Youn-Jae

AU - Bhore, Rafia

AU - Mendez, Patricia

AU - Hughes, Eric

AU - Noviello, Stephanie

PY - 2016

Y1 - 2016

N2 - Background Aims: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV). Methods: Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes. Results: In the Japanese phase 3 study, SVR12 was achieved by 91 of patients with cirrhosis (n = 22) and 84 of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84 of patients with cirrhosis (n = 206) and by 85 of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5–4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation. Conclusions: The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.

AB - Background Aims: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV). Methods: Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes. Results: In the Japanese phase 3 study, SVR12 was achieved by 91 of patients with cirrhosis (n = 22) and 84 of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84 of patients with cirrhosis (n = 206) and by 85 of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5–4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation. Conclusions: The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.

KW - cirrhosis

KW - direct acting antiviral

KW - hepatitis C

KW - safety

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U2 - 10.1111/liv.13049

DO - 10.1111/liv.13049

M3 - Article

VL - 36

SP - 954

EP - 962

JO - Liver International

JF - Liver International

SN - 1478-3223

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