The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world : a comprehensive analysis of a prospective multicenter study
BACKGROUND: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment.
METHODS: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed.
RESULTS: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10-5; genotype 2 vs. 3, p = 3.28 × 10-5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10-5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10-5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10-18) patients.
CONCLUSIONS: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Hepatology international - 14(2020), 2 vom: 03. März, Seite 225-238 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nozaki, Akito [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.01.2021 Date Revised 25.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12072-020-10019-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30720037X |
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| 100 | 1 | |a Nozaki, Akito |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world |b a comprehensive analysis of a prospective multicenter study |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 25.01.2021 | ||
| 500 | |a Date Revised 25.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment | ||
| 520 | |a METHODS: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed | ||
| 520 | |a RESULTS: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10-5; genotype 2 vs. 3, p = 3.28 × 10-5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10-5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10-5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10-18) patients | ||
| 520 | |a CONCLUSIONS: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Chronic hepatitis C | |
| 650 | 4 | |a Glecaprevir | |
| 650 | 4 | |a Multicenter study | |
| 650 | 4 | |a Pibrentasvir | |
| 650 | 4 | |a Refractory factors | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Benzimidazoles |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a Pyrrolidines |2 NLM | |
| 650 | 7 | |a Quinoxalines |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a glecaprevir and pibrentasvir |2 NLM | |
| 700 | 1 | |a Atsukawa, Masanori |e verfasserin |4 aut | |
| 700 | 1 | |a Kondo, Chisa |e verfasserin |4 aut | |
| 700 | 1 | |a Toyoda, Hidenori |e verfasserin |4 aut | |
| 700 | 1 | |a Chuma, Makoto |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamuta, Makoto |e verfasserin |4 aut | |
| 700 | 1 | |a Uojima, Haruki |e verfasserin |4 aut | |
| 700 | 1 | |a Takaguchi, Koichi |e verfasserin |4 aut | |
| 700 | 1 | |a Ikeda, Hiroki |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Tsunamasa |e verfasserin |4 aut | |
| 700 | 1 | |a Ogawa, Shintaro |e verfasserin |4 aut | |
| 700 | 1 | |a Itokawa, Norio |e verfasserin |4 aut | |
| 700 | 1 | |a Arai, Taeang |e verfasserin |4 aut | |
| 700 | 1 | |a Hiraoka, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Asano, Toru |e verfasserin |4 aut | |
| 700 | 1 | |a Fujioka, Shinichi |e verfasserin |4 aut | |
| 700 | 1 | |a Ikegami, Tadashi |e verfasserin |4 aut | |
| 700 | 1 | |a Shima, Toshihide |e verfasserin |4 aut | |
| 700 | 1 | |a Ogawa, Chikara |e verfasserin |4 aut | |
| 700 | 1 | |a Akahane, Takehiro |e verfasserin |4 aut | |
| 700 | 1 | |a Shimada, Noritomo |e verfasserin |4 aut | |
| 700 | 1 | |a Fukunishi, Shinya |e verfasserin |4 aut | |
| 700 | 1 | |a Abe, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Tsubota, Akihito |e verfasserin |4 aut | |
| 700 | 1 | |a Genda, Takuya |e verfasserin |4 aut | |
| 700 | 1 | |a Okubo, Hironao |e verfasserin |4 aut | |
| 700 | 1 | |a Mikami, Shigeru |e verfasserin |4 aut | |
| 700 | 1 | |a Morishita, Asahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Moriya, Akio |e verfasserin |4 aut | |
| 700 | 1 | |a Tani, Joji |e verfasserin |4 aut | |
| 700 | 1 | |a Tachi, Yoshihiko |e verfasserin |4 aut | |
| 700 | 1 | |a Hotta, Naoki |e verfasserin |4 aut | |
| 700 | 1 | |a Ishikawa, Toru |e verfasserin |4 aut | |
| 700 | 1 | |a Okanoue, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Yasuhito |e verfasserin |4 aut | |
| 700 | 1 | |a Kumada, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Iwakiri, Katsuhiko |e verfasserin |4 aut | |
| 700 | 1 | |a Maeda, Shin |e verfasserin |4 aut | |
| 700 | 0 | |a KTK49 Liver Study Group |e verfasserin |4 aut | |
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