title: Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus.
abstract: OBJECTIVE
  Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients.
  
  
  METHODS
  In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected.
  
  
  RESULTS
  The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir.
  
  
  CONCLUSIONS
  Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
authors: Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Wan-Long
authors: WL
authors: Chuang
authors: Liver Research Unit, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan.
authors: Rong-Nan
authors: RN
authors: Chien
authors: Department of Internal Medicine, School of Medicine, China Medical University, Taichung, Taiwan.
authors: Cheng-Yuan
authors: CY
authors: Peng
authors: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
authors: Ting-Tsung
authors: TT
authors: Chang
authors: Department of Medicine, E-Da Hospital, Kaohsiung, Taiwan.
authors: Gin-Ho
authors: GH
authors: Lo
authors: Chang Gung Memorial Hospital and Medical College, Chang Gung University, Taoyuan, Taiwan.
authors: I-Shyan
authors: IS
authors: Sheen
authors: Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
authors: Horng-Yuan
authors: HY
authors: Wang
authors: Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan.
authors: Jyh-Jou
authors: JJ
authors: Chen
authors: Gilead Sciences, Inc., Foster City, California, USA.
authors: Jenny C
authors: JC
authors: Yang
authors: Gilead Sciences, Inc., Foster City, California, USA.
authors: Steven J
authors: SJ
authors: Knox
authors: Gilead Sciences, Inc., Foster City, California, USA.
authors: Bing
authors: B
authors: Gao
authors: Gilead Sciences, Inc., Foster City, California, USA.
authors: Kimberly L
authors: KL
authors: Garrison
authors: Gilead Sciences, Inc., Foster City, California, USA.
authors: Hongmei
authors: H
authors: Mo
authors: Gilead Sciences, Inc., Foster City, California, USA.
authors: Phillip S
authors: PS
authors: Pang
authors: Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan.
authors: Yu-Chun
authors: YC
authors: Hsu
authors: Chang Gung Medical Foundation, Kaohsiung, Taiwan.
authors: Tsung-Hui
authors: TH
authors: Hu
authors: Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan.
authors: Chi-Jen
authors: CJ
authors: Chu
authors: National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
authors: Jia-Horng
authors: JH
authors: Kao
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage*; D002219:Carbamates / Q000008:administration & dosage*; D004338:Drug Combinations; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir / Q000008:administration & dosage*; D013607:Tablets; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D004338:Drug Combinations; D005449:Fluorenes; D006576:Heterocyclic Compounds, 4 or More Rings; D013607:Tablets; C000611331:sofosbuvir-velpatasvir drug combination; C586541:ledipasvir; D000069474:Sofosbuvir
keywords: Taiwan; hepatitis C virus (HCV); infection; ledipasvir; sofosbuvir