High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world

Pérez, Ana Belén Macho; Chueca, Natalia; García-Deltoro, Miguel; Martínez-Sapiña, Ana; Lara-Pérez, María Magdalena; García‐Bujalance, Silvia; Aldámiz‐Echevarría, Teresa; Vera-Méndez, Francisco Jesús; Pineda, Juan A.; Casado, Marta; Pascasio, J.M.; Salmerón, Javier; Alados-Arboledas, Juan Carlos; Poyato, Antonio; Téllez, Francisco Ayuga; Rivero‐Juárez, Antonio; Merino, Dolores; Vivancos-Gallego, María Jesús; Rosales-Zábal, José Miguel; García, Féderico; Ocete, María Dolores; Simón, Miguel Ángel; Rincón, Pilar; Reus, Sergi; Iglesia, Alberto de la; García-Arata, Isabel; Jiménez, Miguel; Jiménez, Fernando; Hernández-Quero, José; Galera, Carlos; Balghata, Mohamed Omar; Primo, J; Masiá, Mar; Espinosa, Núria; Delgado, Marcial; von-Wichmann, Miguel Ángel; Collado, Antonio; Santos, Jesús; Mínguez, Carlos; Díaz‐Flores, Felicitas; Fernández, Elisa; Bernal, Enrique; Juan, José de; Antón, J.; Vélez, Mónica; Aguilera, Antonio; Navarro, Daniel; Arenas, Juan; Fernández, Clotilde; Espinosa, María Dolores; Rios, María; Alonso, Roberto; Hidalgo, Carmen; Hernández, Rosario; Téllez, María J.; Rodríguez, Francisco Javier; Antequera, Pedro; Delgado, Cristina; Martin, Patrícia; Crespo, Javier; Becerril, Berta; Pérez, Óscar; Garcı́a-Herola, Antonio; Montero, J.L.; Freyre, Carolina; Grau, Concepción

doi:10.1016/j.jhep.2019.06.022

Cited by 13 publications

(5 citation statements)

References 21 publications

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“…In addition, the general tendency before approval of VOX/VEL/SOF was to re-treat patients only with high urgency caused by advanced liver disease [26]. In line with the observation from other cohorts [27,28], patients in the present study who received rescue therapy in comparison to patients who did not receive re-treatment more often had liver cirrhosis (52.6 % versus 42.9 %, respectively).…”

Section: Discussionsupporting

confidence: 85%

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

et al. 2020

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Background Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described. Patients and methods Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available. Results Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %). Conclusions Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.

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Section: Discussionsupporting

confidence: 85%

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

et al. 2020

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“…Lower cure rates were observed for those retreated with other regimens (PP SVR12 76–79%) in REACH‐C. Sequencing guided retreatment for virological failure with extended duration first‐line regimens can provide cure rates comparable to SOF/VEL/VOX 41 ; however, this approach is resource intensive, requiring specialist expertise and infrastructure not readily available in many settings. Sequencing was performed in a minority of virological failures within REACH‐C, even in the setting of second treatment failure.…”

Section: Discussionmentioning

confidence: 99%

Retreatment for hepatitis C virus direct‐acting antiviral therapy virological failure in primary and tertiary settings: The REACH‐C cohort

Carson

Hajarizadeh

Hanson

et al. 2022

Journal of Viral Hepatitis

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Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n = 10,843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n = 56) and tertiary (n = 157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…16,[19][20][21] In moderately resource-limiting settings where these new regimens may not be available, a resistance-guided retreatment approach using first-generation DAAs with a switch of the DAA drug class and additional RBV with or without extended duration is a workable option. 8,22,23 Circulating HCV displays a high degree of genetic heterogeneity; variants with every possible individual substitution are generated daily. 24 Under suboptimal drug concentrations, drugresistant variants are rapidly enriched, leading to viral breakthrough or relapse.…”

Section: Discussionmentioning

confidence: 99%

High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world

Cited by 13 publications

References 21 publications

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

Retreatment for hepatitis C virus direct‐acting antiviral therapy virological failure in primary and tertiary settings: The REACH‐C cohort

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

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