Abstract
Background/purpose: In Japan, there is a growing population of patients with chronic hepatitis C virus (HCV) infection who failed a direct-acting antiviral (DAA)-based regimen. In this Phase 3 study, we evaluated sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 HCV infection who previously received DAAs. Methods: Patients were randomized 1:1 to receive sofosbuvir–velpatasvir plus ribavirin for 12 or 24 weeks. Randomization was stratified by HCV genotype and presence of cirrhosis. The primary endpoint was sustained virologic response 12-week post-treatment (SVR12). Results: Of 117 participants, 81% had HCV genotype 1 infection, 33% had cirrhosis, and 95% had NS5A resistance-associated substitutions (RAS) at baseline. Overall, SVR12 rates were 97% (58/60; 95% CI 88–100%) with 24 weeks of treatment and 82% (47/57; 95% CI 70–91%) with 12 weeks. For HCV genotype 1 and 2 infected patients, the SVR12 rates with 24 weeks of treatment were 98% and 92%, respectively. In both treatment groups, SVR12 rates in HCV genotype 1 patients were statistically superior to a historical control rate of 50% (p < 0.001). For patients with NS5A RASs at baseline, 85% (46/54) in the 12-week group and 96% (54/56) in the 24-week group achieved SVR12. The most common adverse events were upper respiratory tract viral infection, anemia, and headache. Three (2.6%) patients discontinued treatment because of adverse events. Conclusion: Sofosbuvir–velpatasvir plus ribavirin was highly effective and well tolerated in Japanese patients who previously failed a DAA-based regimen. Baseline NS5A RASs did not affect treatment outcomes.
| Original language | English |
|---|---|
| Journal | Hepatology International |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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Keywords
- Antiviral resistance
- DAA-experienced
- NS5A inhibitor
- NS5B polymerase inhibitor
- Salvage therapy
ASJC Scopus subject areas
- Hepatology
Cite this
Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals. / Izumi, Namiki; Takehara, Tetsuo; Chayama, Kazuaki; Yatsuhashi, Hiroshi; Takaguchi, Koichi; Ide, Tatsuya; Kurosaki, Masayuki; Ueno, Yoshiyuki; Toyoda, Hidenori; Kakizaki, Satoru; Tanaka, Yasuhito; Kawakami, Yoshiiku; Enomoto, Hirayuki; Ikeda, Fusao; Jiang, Deyuan; De-Oertel, Shampa; McNabb, Brian L.; Camus, Gregory; Stamm, Luisa M.; Brainard, Diana M.; McHutchison, John G.; Mochida, Satoshi; Mizokami, Masashi.
In: Hepatology International, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals
AU - Izumi, Namiki
AU - Takehara, Tetsuo
AU - Chayama, Kazuaki
AU - Yatsuhashi, Hiroshi
AU - Takaguchi, Koichi
AU - Ide, Tatsuya
AU - Kurosaki, Masayuki
AU - Ueno, Yoshiyuki
AU - Toyoda, Hidenori
AU - Kakizaki, Satoru
AU - Tanaka, Yasuhito
AU - Kawakami, Yoshiiku
AU - Enomoto, Hirayuki
AU - Ikeda, Fusao
AU - Jiang, Deyuan
AU - De-Oertel, Shampa
AU - McNabb, Brian L.
AU - Camus, Gregory
AU - Stamm, Luisa M.
AU - Brainard, Diana M.
AU - McHutchison, John G.
AU - Mochida, Satoshi
AU - Mizokami, Masashi
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background/purpose: In Japan, there is a growing population of patients with chronic hepatitis C virus (HCV) infection who failed a direct-acting antiviral (DAA)-based regimen. In this Phase 3 study, we evaluated sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 HCV infection who previously received DAAs. Methods: Patients were randomized 1:1 to receive sofosbuvir–velpatasvir plus ribavirin for 12 or 24 weeks. Randomization was stratified by HCV genotype and presence of cirrhosis. The primary endpoint was sustained virologic response 12-week post-treatment (SVR12). Results: Of 117 participants, 81% had HCV genotype 1 infection, 33% had cirrhosis, and 95% had NS5A resistance-associated substitutions (RAS) at baseline. Overall, SVR12 rates were 97% (58/60; 95% CI 88–100%) with 24 weeks of treatment and 82% (47/57; 95% CI 70–91%) with 12 weeks. For HCV genotype 1 and 2 infected patients, the SVR12 rates with 24 weeks of treatment were 98% and 92%, respectively. In both treatment groups, SVR12 rates in HCV genotype 1 patients were statistically superior to a historical control rate of 50% (p < 0.001). For patients with NS5A RASs at baseline, 85% (46/54) in the 12-week group and 96% (54/56) in the 24-week group achieved SVR12. The most common adverse events were upper respiratory tract viral infection, anemia, and headache. Three (2.6%) patients discontinued treatment because of adverse events. Conclusion: Sofosbuvir–velpatasvir plus ribavirin was highly effective and well tolerated in Japanese patients who previously failed a DAA-based regimen. Baseline NS5A RASs did not affect treatment outcomes.
AB - Background/purpose: In Japan, there is a growing population of patients with chronic hepatitis C virus (HCV) infection who failed a direct-acting antiviral (DAA)-based regimen. In this Phase 3 study, we evaluated sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 HCV infection who previously received DAAs. Methods: Patients were randomized 1:1 to receive sofosbuvir–velpatasvir plus ribavirin for 12 or 24 weeks. Randomization was stratified by HCV genotype and presence of cirrhosis. The primary endpoint was sustained virologic response 12-week post-treatment (SVR12). Results: Of 117 participants, 81% had HCV genotype 1 infection, 33% had cirrhosis, and 95% had NS5A resistance-associated substitutions (RAS) at baseline. Overall, SVR12 rates were 97% (58/60; 95% CI 88–100%) with 24 weeks of treatment and 82% (47/57; 95% CI 70–91%) with 12 weeks. For HCV genotype 1 and 2 infected patients, the SVR12 rates with 24 weeks of treatment were 98% and 92%, respectively. In both treatment groups, SVR12 rates in HCV genotype 1 patients were statistically superior to a historical control rate of 50% (p < 0.001). For patients with NS5A RASs at baseline, 85% (46/54) in the 12-week group and 96% (54/56) in the 24-week group achieved SVR12. The most common adverse events were upper respiratory tract viral infection, anemia, and headache. Three (2.6%) patients discontinued treatment because of adverse events. Conclusion: Sofosbuvir–velpatasvir plus ribavirin was highly effective and well tolerated in Japanese patients who previously failed a DAA-based regimen. Baseline NS5A RASs did not affect treatment outcomes.
KW - Antiviral resistance
KW - DAA-experienced
KW - NS5A inhibitor
KW - NS5B polymerase inhibitor
KW - Salvage therapy
UR - http://www.scopus.com/inward/record.url?scp=85050319613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050319613&partnerID=8YFLogxK
U2 - 10.1007/s12072-018-9878-6
DO - 10.1007/s12072-018-9878-6
M3 - Article
C2 - 30030720
AN - SCOPUS:85050319613
JO - Hepatology International
JF - Hepatology International
SN - 1936-0533
ER -