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

被引：82

作者：

Llaneras, Jordi ^{[1
]}

Riveiro-Barciela, Mar ^{[1
,2
]}

Lens, Sabela ^{[2
,3
]}

Diago, Moises ^{[4
]}

Cachero, Alba ^{[5
]}

Garcia-Samaniego, Javier ^{[2
,6
]}

Conde, Isabel ^{[7
]}

Arencibia, Ana ^{[8
]}

Arenas, Juan ^{[9
]}

Gea, Francisco ^{[10
]}

Torras, Xavier ^{[2
,11
]}

Luis Calleja, Jose ^{[12
]}

Antonio Carrion, Jose ^{[13
]}

Fernandez, Inmaculada ^{[14
]}

Maria Morillas, Rosa ^{[2
,15
]}

Miguel Rosales, Jose ^{[16
]}

Carmona, Isabel ^{[17
]}

Fernandez-Rodriguez, Conrado ^{[18
]}

Hernandez-Guerra, Manuel ^{[19
]}

Llerena, Susana ^{[20
]}

Bernal, Vanesa ^{[21
]}

Turnes, Juan ^{[22
]}

Gonzalez-Santiago, Jesus M. ^{[23
]}

Montoliu, Silvia ^{[24
]}

Figueruela, Blanca ^{[25
]}

Badia, Ester ^{[26
]}

Delgado, Manuel ^{[27
]}

Fernandez-Bermejo, Miguel ^{[28
]}

Inarrairaegui, Mercedes ^{[2
,29
]}

Manuel Pascasio, Juan ^{[2
,30
]}

Esteban, Rafael ^{[1
,2
]}

Marino, Zoe ^{[2
,3
]}

Buti, Maria ^{[1
,2
]}

机构：

[1] UAB, Dept Med, Hosp Univ Vall dHebron, Barcelona, Spain

[2] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain

[3] Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain

[4] Hosp Gen Univ Valencia, Valencia, Spain

[5] Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain

[6] Hosp Univ La Paz, IdiPAZ, Madrid, Spain

[7] Hosp Univ & Politecn La Fe Valencia, Valencia, Spain

[8] Hosp Univ Nuestra Senora La Candelaria, Santa Cruz De Tenerife, Spain

[9] Hosp Univ Donostia, Donostia San Sebastian, Spain

[10] Hosp Ramon & Cajal, Madrid, Spain

[11] Hosp Univ Santa Creu & St Pau, Barcelona, Spain

[12] Hosp Univ Puerta Hierro, Madrid, Spain

[13] UAB, IMIM Hosp Mar Med Res Inst, Hosp Mar, Liver Sect,Gastroenterol Dept, Barcelona, Spain

[14] Hosp 12 Octubre, Madrid, Spain

[15] Hosp Univ Germans Trias i Pujol, Badalona, Spain

[16] Hosp Costa Sol, Malaga, Spain

[17] Hosp Virgen Macarena, Seville, Spain

[18] Hosp Univ Fdn Alcorcon, Madrid, Spain

[19] Hosp Univ Canarias, Santa Cruz De Tenerife, Spain

[20] Hosp Univ Marques de Valdecilla, Santander, Spain

[21] Hosp Miguel Servet, Zaragoza, Spain

[22] Complejo Hosp Univ Pontevedra, Pontevedra, Spain

[23] Complejo Asistencial Univ Salamanca, Salamanca, Spain

[24] Hosp Joan 23, Tarragona, Spain

[25] Hosp Virgen Valme, Seville, Spain

[26] Hosp Univ Burgos, Burgos, Spain

[27] Hosp Univ A Coruna, La Coruna, Spain

[28] Hosp Univ San Pedro de Alcantara, Caceres, Spain

[29] Inst Invest Sanitaria Navarra IdiSNA, Clin Univ Navarra, Navarra, Spain

[30] Hosp Univ Virgen Rocio, Seville, Spain

来源：

JOURNAL OF HEPATOLOGY | 2019年 / 71卷 / 04期

关键词：

Sofosbuvir; Velpatasvir; Voxilaprevir; Hepatitis C; Treatment failures; HCV genotype 3; TREATMENT-EXPERIENCED PATIENTS; SOFOSBUVIR PLUS VELPATASVIR; VIRUS-INFECTION; ANTIVIRAL DRUGS; GENOTYPES; HCV; VOXILAPREVIR; RETREATMENT; SOF/VEL/VOX; EFFICACY;

D O I：

10.1016/j.jhep.2019.06.002

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：666 / 672

页数：7

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