Initial- and re-treatment effectiveness of glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C virus-genotype 1/2/3 infections.

Abstract

BACKGROUND:

Glecaprevir and pibrentasvir (GLE/PIB) are potent antiviral agents for hepatitis C virus (HCV) pan-genotypic infections; however, their clinical effectiveness and safety remain limited in the real-world. This study aimed to evaluate viral responses and the safety of GLE/PIB for patients with chronic HCV-1/2/3 infections during both initial- (Arm A) and re-treatment (Arm B) with all-oral direct-acting antiviral agents (DAAs).

METHODS:

This prospective-observational cohort study included Japanese patients with chronic HCV-1/2/3 infections (n = 271: 183 in Arm A and 83 in Arm B), who had started receiving GLE/PIB. Primary end point was a sustained virological response (SVR) rate at week 12 (SVR12) after the end of GLE/PIB treatment (EOT).

RESULTS:

SVR12 was achieved by 99.4% of patients (180/181: modified intention-to-treat (mITT) analysis excluding 2 patients lost to follow-up) in Arm A. One patient with an HCV-3b infection who discontinued at week 8 failed to achieve SVR12. SVR12 was achieved by 97.7% of patients (85/87: mITT excluding 1 patient lost to follow-up) in Arm B. Virological relapse occurred in 2 patients with HCV-1b, presenting common 5 loci of resistance-associated substitutions (RASs) including A92 RASs in the NS5A lesion at baseline. Any adverse events (AEs) (grade ≥ 3) occurred in 8 patients (3.0%). 8 patients (3.0%) discontinued due to AEs, however, all of them achieved SVR12.

CONCLUSIONS:

Initial and re-treatment with GLE/PIB are effective and safe for Japanese patients with HCV-1/2/3 in real-life settings. Further studies are required to elucidate the mechanism underlying treatment failures of GLE/PIB to completely eradicate HCV worldwide.

• Authors: Hitomi Sezaki, Fumitaka Suzuki, Tetsuya Hosaka, Shunichirou Fujiyama, Yusuke Kawamura, Norio Akuta, Masahiro Kobayashi, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 54 Issue 10 Pg. 916-927 (Oct 2019) ISSN: 1435-5922 [Electronic] Japan
• PMID: 30903385 (Publication Type: Journal Article, Observational Study)

Chemical References

• Antiviral Agents
• Benzimidazoles
• Drug Combinations
• Pyrrolidines
• Quinoxalines
• RNA, Viral
• Sulfonamides
• glecaprevir and pibrentasvir

Topics

• Aged
• Antiviral Agents (administration & dosage, adverse effects, therapeutic use)
• Benzimidazoles (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Drug Combinations
• Drug Resistance, Viral
• Female
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Liver Cirrhosis (virology)
• Male
• Middle Aged
• Prospective Studies
• Pyrrolidines (administration & dosage, adverse effects, therapeutic use)
• Quinoxalines (administration & dosage, adverse effects, therapeutic use)
• RNA, Viral (blood)
• Retreatment (adverse effects, methods)
• Sulfonamides (administration & dosage, adverse effects, therapeutic use)
• Sustained Virologic Response
• Treatment Outcome