Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort

Fecha de publicación: 01/06/2017

Autores de IIS La Fe

María García Eliz

Autor

Participantes ajenos a IIS La Fe

Calleja, JL
Crespo, J
Rincon, D
Ruiz-Antoran, B
Fernandez, I
Perello, C
Gea, F
Lens, S
Garcia-Samaniego, J
Sacristan, B
Llerena, S
Pascasio, JM
Turnes, J
Torras, X
Morillas, RM
Llaneras, J
Serra, MA
Diago, M
Rodriguez, CF
Ampuero, J
Jorquera, F
Simon, MA
Arenas, J
Navascues, CA
Bañares R
Muñoz R
Albillos, A
Mariño Z
Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collab

Grupos

Hepatología, Cirugia Hepatobiliopancreática y Trasplantes

Leader

Marina Berenguer Haym

Abstract

Background & Aims: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/rito navir plus dasabuvir (OMV/PTV/r + DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. Methods: Data from HCV genotype 1 patients treated with either OMV/PTV/r + DSV +/- ribavirin (RBV) (n = 1567) or LDV/SOF +/- RBV (n = 1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. Results: The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV +/- RBV and 95.8% with LDV/SOF +/- RBV. No significant differences were observed in SVR according to HCV subgenotype (p = 0.321 [OMV/PTV/r + DSV +/- RBV] and p = 0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV +/- RBV] and p = 0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p < 0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r + DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. Conclusions: In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r + DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. Lay summary: In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex. (c) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Datos de la publicación

ISSN/ISSNe:: 0168-8278, 1600-0641
Tipo:: Article
Páginas:: 1138-1148
DOI:: 10.1016/j.jhep.2017.01.028
PubMed:: 28189751
Factor de Impacto:: 5,633 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

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Métricas

Filiaciones

Calleja, JL:: Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid and CIBERehd, Madrid, Spain

Univ Autonoma Madrid, Hosp Univ Puerta de Hierro, Madrid, Spain

CIBERehd, Madrid, Spain
Crespo, J:: Hospital Universitario Marques de Valdecilla, IDIVAL, Santander and Facultad de Medicina, Universidad de Cantabria, Spain

Hosp Univ Marques de Valdecilla, IDIVAL, Santander, Cantabria, Spain

Univ Cantabria, Fac Med, Santander, Spain
Rincon, D:: Hospital General Universitario Gregorio Marañón, Facultad de Medicina de la Universidad Complutense and CIBERehd, Madrid, Spain

Univ Complutense, Hosp Gen Univ Gregorio Maranon, Fac Med, Madrid, Spain
Ruiz-Antoran, B:: Hospital Universitario Puerta de Hierro, Madrid, Spain

CIBERehd, Madrid, Spain

Hosp Univ Puerta de Hierro, Madrid, Spain
Fernandez, I:: Hospital Universitario 12 de Octubre, Madrid, Spain

Hosp Univ 12 Octubre, Madrid, Spain
Perello, C:: Hospital Universitario Puerta de Hierro, Madrid, Spain

CIBERehd, Madrid, Spain

Hosp Univ Puerta de Hierro, Madrid, Spain
Gea, F:: Hospital Universitario Ramón y Cajal, Madrid, Spain

Hosp Univ Ramon & Cajal, Madrid, Spain
Lens, S:: Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain

Hosp Clin Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
Garcia-Samaniego, J:: Hospital Universitario La Paz, CIBERehd, IdiPAZ, Madrid, Spain

Hosp Univ La Paz, CIBERehd, IdiPAZ, Madrid, Spain
Sacristan, B:: Hospital San Pedro, Logroño, Spain

Hosp San Pedro, Logrono, Spain
Garcia-Eliz, M:: Hospital Universitario La Fe and CIBERehd, Valencia, Spain

Hosp Univ La Fe, Valencia, Spain

Ciberehd, Valencia, Spain
Llerena, S:: Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Cantabria, Spain

Hosp Univ Marques de Valdecilla, IDIVAL, Santander, Cantabria, Spain
Pascasio, JM:: Hospital Universitario Virgen del Rocío and CIBERehd, Seville, Spain

Hosp Univ Virgen del Rocio, Seville, Spain

CIBERehd, Seville, Spain
Turnes, J:: Complejo Hospitalario Universitario de Pontevedra and IISGS, Spain

Complejo Hosp Univ Pontevedra, Casas Novas, Pontevedra, Spain

IISGS, Vigo, Pontevedra, Spain
Torras, X:: Hospital Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain

Hosp Santa Creu & Sant Pau, Barcelona, Spain

CIBEREHD, Barcelona, Spain
Morillas, RM:: Hospital Germans Trias i Pujol and CIBERehd, Badalona, Spain

Hosp Badalona Germans Trias & Pujol, Badalona, Spain

CIBERehd, Badalona, Spain
Llaneras, J:: Hospital Universitario Vall D'Hebrón, Barcelona, Spain

Hosp Univ Vall dHebron, Barcelona, Spain
Serra, MA:: Hospital Clinico de Valencia, Valencia, Spain

Hosp Clin Valencia, Valencia, Spain
Diago, M:: Hospital Universitario General de Valencia, Valencia, Spain

Hosp Univ Gen Valencia, Valencia, Spain
Rodriguez, CF:: Hospital Universitario Fundación Alcorcon, Madrid, Spain

Hosp Univ Fdn Alcorcon, Madrid, Spain
Ampuero, J:: Hospital Universitario Virgen del Rocío, IBIS and CIBERehd, Spain

CIBERehd, Seville, Spain

Hosp Univ Virgen del Rocio, IBIS, Seville, Spain
Jorquera, F:: Complejo Asistencial Universitario León, León, IBIOMED and CIBERehd, Spain

Complejo Asistencial Univ Leon, IBIOMED, Leon, Spain

CIBERehd, Leon, Spain
Simon, MA:: Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

Hosp Clin Univ Lozano Blesa, Zaragoza, Spain
Arenas, J:: Hospital Universitario Donostia, San Sebastián, Spain

Hosp Univ Donostia, San Sebastian, Spain
Navascues, CA:: Hospital Universitario Central de Asturias, Oviedo, Spain

Hosp Univ Cent Asturias, Oviedo, Spain
Bañares R:: Hospital General Universitario Gregorio Marañón, Facultad de Medicina de la Universidad Complutense and CIBERehd, Madrid, Spain
Muñoz R:: Hospital Universitario 12 de Octubre, Madrid, Spain
Albillos, A:: Hospital Universitario Ramón y Cajal, Madrid, Spain

Hosp Univ Ramon & Cajal, Madrid, Spain
Mariño Z:: Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collab:: Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collab

Keywords

Hepatitis C; Chronic; Genotype 1; Ombitasvir; Paritaprevir; Ritonavir; Dasabuvir; Ledipasvir; Sofosbuvir; Real-world; Antiviral agents; Sustained virologic response; Randomized controlled trials