Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals

Namiki Izumi, Tetsuo Takehara, Kazuaki Chayama, Hiroshi Yatsuhashi, Koichi Takaguchi, Tatsuya Ide, Masayuki Kurosaki, Yoshiyuki Ueno, Hidenori Toyoda, Satoru Kakizaki, Yasuhito Tanaka, Yoshiiku Kawakami, Hirayuki Enomoto, Fusao Ikeda, Deyuan Jiang, Shampa De-Oertel, Brian L. McNabb, Gregory Camus, Luisa M. Stamm, Diana M. BrainardJohn G. McHutchison, Satoshi Mochida, Masashi Mizokami

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish
JournalHepatology International
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Ribavirin
Hepatitis C
Antiviral Agents
Genotype
Hepacivirus
Virus Diseases
Therapeutics
Fibrosis
Chronic Hepatitis C
Random Allocation
Respiratory Tract Infections
Headache
Anemia
Japan
Sustained Virologic Response

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 journalArticle

Izumi, N, Takehara, T, Chayama, K, Yatsuhashi, H, Takaguchi, K, Ide, T, Kurosaki, M, Ueno, Y, Toyoda, H, Kakizaki, S, Tanaka, Y, Kawakami, Y, Enomoto, H, Ikeda, F, Jiang, D, De-Oertel, S, McNabb, BL, Camus, G, Stamm, LM, Brainard, DM, McHutchison, JG, Mochida, S & Mizokami, M 2018, 'Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals', Hepatology International. https://doi.org/10.1007/s12072-018-9878-6
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. / Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals. In: Hepatology International. 2018.
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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

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