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

21 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
Pages (from-to)356-367
Number of pages12
JournalHepatology International
Volume12
Issue number4
DOIs
Publication statusPublished - Jul 1 2018

Keywords

  • Antiviral resistance
  • DAA-experienced
  • NS5A inhibitor
  • NS5B polymerase inhibitor
  • Salvage therapy

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals'. Together they form a unique fingerprint.

  • Cite this

    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, B. L., Camus, G., Stamm, L. M., ... Mizokami, M. (2018). Sofosbuvir–velpatasvir plus ribavirin in Japanese patients with genotype 1 or 2 hepatitis C who failed direct-acting antivirals. Hepatology International, 12(4), 356-367. https://doi.org/10.1007/s12072-018-9878-6