title: Ribavirin-Free Regimen With Sofosbuvir and Velpatasvir Is Associated With High Efficacy and Improvement of Patient-Reported Outcomes in Patients With Genotypes 2 and 3 Chronic Hepatitis C: Results From Astral-2 and -3 Clinical Trials.
abstract: Until recently, the approved treatment regimens for patients with hepatitis C virus (HCV) genotypes (GTs) 2 and 3 contain sofosbuvir (SOF) and ribavirin (RBV) for 12 or 24 weeks. The impact of RBV-free pan-genotypic regimen with SOF and velpatasvir (SOF/VEL) on patient-reported outcomes (PROs) of patients with genotype 2 and 3 has not been described.
  
  
  
  PROs data were collected from participants of ASTRAL-2 and ASTRAL-3 studies before, during, and after treatment using 4 PRO instruments (Short Form-36, Chronic Liver Disease Questionnaire-HCV, Functional Assessment of Chronic Illness Therapy-Fatigue, and Work Productivity and Activity Index: Specific Health Problem), and compared between the SOF/VEL and SOF + RBV groups.
  
  
  
  A total of 818 HCV patients were included: 78% treatment naive, 25% cirrhosis. The rates of nearly all adverse events were lower in the RBV-free SOF/VEL group (all P < .03). The SOF/VEL group also experienced improvement of their PROs by treatment week 4 (+1.8% on average across all PROs), which continued throughout treatment (+4.1%) and post-treatment (+5.5%). In contrast, those in the SOF + RBV group had a modest decline in their PROs starting at treatment week 4 (up to -3.7%), which lasted until the end of treatment (up to -6.4%). In multiple regression analysis, the association of a treatment regimen with end-of-treatment PROs was significant for nearly all PROs; the average beta was +5.0% for the use of SOF/VEL (reference: SOF + RBV).
  
  
  
  Patients receiving ribavirin-free SOF/VEL reported significantly better PRO scores during treatment compared with those receiving the RBV-containing regimen. Furthermore, the interferon- and ribavirin-free SOF/VEL regimen resulted in a rapid improvement of PROs in HCV GTs 2 and 3 patients during treatment and after achieving sustained virologic response.
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Center for Outcomes Research in Liver Disease, Washington D.C.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
authors.affiliation: Queen Mary University London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Rush University Medical Center, Chicago, Illinois.
authors.forename: Nancy
authors.initials: N
authors.lastname: Reau
authors.affiliation: Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: University of Toronto Health Network, Ontario, Canada.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: James J. Peters Veterans Affairs Medical Center, Bronx, New York.
authors.forename: Norbert
authors.initials: N
authors.lastname: Bräu
authors.affiliation: Alfred Health and Monash University, Melbourne, Australia.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.affiliation: Center for Outcomes Research in Liver Disease, Washington D.C.
authors.forename: Fatema
authors.initials: F
authors.lastname: Nader
authors.affiliation: Center for Outcomes Research in Liver Disease, Washington D.C.
authors.forename: Linda
authors.initials: L
authors.lastname: Henry
authors.affiliation: Center for Outcomes Research in Liver Disease, Washington D.C.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hunt
mesh_terms: D000328:Adult; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005260:Female; 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 / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D002219:Carbamates; D006576:Heterocyclic Compounds, 4 or More Rings; D012254:Ribavirin; D000069474:Sofosbuvir; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans
keywords: direct-acting antivirals; fatigue; health-related quality of life; hepatitis C; work productivity