Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study.
Aminoisobutyric Acids
Antiviral Agents
/ therapeutic use
Benzimidazoles
Cyclopropanes
Follow-Up Studies
Genotype
Hepacivirus
/ genetics
Hepatitis C, Chronic
/ complications
Humans
Lactams, Macrocyclic
Leucine
/ analogs & derivatives
Male
Neoplasm Recurrence, Local
Proline
/ analogs & derivatives
Pyrrolidines
Quinoxalines
/ therapeutic use
Sulfonamides
Sustained Virologic Response
glecaprevir
hepatitis C
pibrentasvir
sustained virologic response
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
14
01
2022
received:
20
08
2021
accepted:
16
02
2022
pubmed:
28
2
2022
medline:
11
6
2022
entrez:
27
2
2022
Statut:
ppublish
Résumé
This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens. M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance-associated substitutions and safety outcomes related to liver progression were also assessed. Of 384 participants enroled, 377 participants were included in the as-observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non-responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment-experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re-infected and one experienced late relapse at post-treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir. Glecaprevir/pibrentasvir demonstrated long-term durability of efficacy after SVR12 was achieved. Hepatic-related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance-associated substitutions.
Sections du résumé
BACKGROUND AND AIMS
This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens.
METHODS
M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance-associated substitutions and safety outcomes related to liver progression were also assessed.
RESULTS
Of 384 participants enroled, 377 participants were included in the as-observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non-responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment-experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re-infected and one experienced late relapse at post-treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir.
CONCLUSIONS
Glecaprevir/pibrentasvir demonstrated long-term durability of efficacy after SVR12 was achieved. Hepatic-related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance-associated substitutions.
Substances chimiques
Aminoisobutyric Acids
0
Antiviral Agents
0
Benzimidazoles
0
Cyclopropanes
0
Lactams, Macrocyclic
0
Pyrrolidines
0
Quinoxalines
0
Sulfonamides
0
pibrentasvir
2WU922TK3L
Proline
9DLQ4CIU6V
Leucine
GMW67QNF9C
glecaprevir
K6BUU8J72P
Banques de données
ClinicalTrials.gov
['NCT02441283']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1278-1286Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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