Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs


Por: Llaneras, J, Riveiro-Barciela, M, Lens, S, Diago, M, Cachero, A, Garcia-Samaniego, J, Conde, I, Arencibia, A, Arenas, J, Gea, F, Torras, X, Calleja, JL, Carrion, JA, Fernandez, I, Morillas, RM, Rosales, JM, Carmona, I, Fernandez-Rodriguez, C, Hernandez-Guerra, M, Llerena, S, Bernal, V, Turnes, J, Gonzalez-Santiago, JM, Montoliu, S, Figueruela, B, Badia, E, Delgado, M, Fernandez-Bermejo, M, Inarrairaegui, M, Pascasio, JM, Esteban, R, Marino, Z, Buti, M

Publicada: 1 oct 2019
Resumen:
Background & Aims: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. Methods: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. Results: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevirtr +dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific. Conclusion: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group. Lay summary: Treatment with sofosbuvirtvelpatasvir/voxilapre vir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile. (C) 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Filiaciones:
Llaneras, J:
 UAB, Dept Med, Hosp Univ Vall dHebron, Barcelona, Spain

Riveiro-Barciela, M:
 UAB, Dept Med, Hosp Univ Vall dHebron, Barcelona, Spain

 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

Lens, S:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain

Diago, M:
 Hosp Gen Univ Valencia, Valencia, Spain

Cachero, A:
 Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain

Garcia-Samaniego, J:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Hosp Univ La Paz, IDIPAZ, Madrid, Spain

Conde, I:
 Hosp Univ & Politecn La Fe Valencia, Valencia, Spain

Arencibia, A:
 Hosp Univ Nuestra Senora La Candelaria, Santa Cruz De Tenerife, Spain

Arenas, J:
 Hosp Univ Donostia, Donostia San Sebastian, Spain

Gea, F:
 Hosp Ramon & Cajal, Madrid, Spain

Torras, X:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Hosp Univ Santa Creu & St Pau, Barcelona, Spain

Calleja, JL:
 Hosp Univ Puerta Hierro, Madrid, Spain

Carrion, JA:
 UAB, IMIM Hosp Mar Med Res Inst, Hosp Mar, Liver Sect,Gastroenterol Dept, Barcelona, Spain

Fernandez, I:
 Hosp 12 Octubre, Madrid, Spain

Morillas, RM:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Hosp Univ Germans Trias i Pujol, Badalona, Spain

Rosales, JM:
 Hosp Costa Sol, Malaga, Spain

Carmona, I:
 Hosp Virgen Macarena, Seville, Spain

Fernandez-Rodriguez, C:
 Hosp Univ Fdn Alcorcon, Madrid, Spain

Hernandez-Guerra, M:
 Hosp Univ Canarias, Santa Cruz De Tenerife, Spain

Llerena, S:
 Hosp Univ Marques de Valdecilla, Santander, Spain

Bernal, V:
 Hosp Miguel Servet, Zaragoza, Spain

Turnes, J:
 Complejo Hosp Univ Pontevedra, Pontevedra, Spain

Gonzalez-Santiago, JM:
 Complejo Asistencial Univ Salamanca, Salamanca, Spain

Montoliu, S:
 Hosp Joan 23, Tarragona, Spain

Figueruela, B:
 Hosp Virgen Valme, Seville, Spain

Badia, E:
 Hosp Univ Burgos, Burgos, Spain

Delgado, M:
 Hosp Univ A Coruna, La Coruna, Spain

Fernandez-Bermejo, M:
 Hosp Univ San Pedro de Alcantara, Caceres, Spain

Inarrairaegui, M:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Inst Invest Sanitaria Navarra IdiSNA, Clin Univ Navarra, Navarra, Spain

Pascasio, JM:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Hosp Univ Virgen Rocio, Seville, Spain

Esteban, R:
 UAB, Dept Med, Hosp Univ Vall dHebron, Barcelona, Spain

 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

Marino, Z:
 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

 Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain

Buti, M:
 UAB, Dept Med, Hosp Univ Vall dHebron, Barcelona, Spain

 Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
ISSN: 01688278
Editorial
ELSEVIER, RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 71 Número: 4
Páginas: 666-672
WOS Id: 000488196300008
ID de PubMed: 31203153
imagen Green Accepted

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