title: Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis.
abstract: The combination of sofosbuvir and velpatasvir is used to treat patients with hepatitis C virus (HCV) infection of different genotypes. We compared the effects of this treatment regimen, with and without ribavirin, on outcomes reported by patients (patient-reported outcomes [PROs]) with HCV infection, with or without cirrhosis.
  
  
  
  We performed a post hoc analysis of data collected from phase 3 clinical trials (ASTRAL-1, -2, -3, and -4) of 1701 patients infected with HCV of different genotypes treated with sofosbuvir and velpatasvir with ribavirin for 12 weeks (n = 87), sofosbuvir with ribavirin for 12 or 24 weeks (n = 401), and ribavirin-free sofosbuvir and velpatasvir for 12 or 24 weeks (n = 1213). In all trials, participants completed 4 PRO questionnaires (while blinded to their HCV RNA levels): the Short Form-36, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Chronic Liver Disease Questionnaire-HCV Version, and the Work Productivity and Activity Impairment: Specific Health Problem, at multiple time points. We compared baseline PROs and changes in PROs following treatment in patients without cirrhosis (n = 1112), with compensated cirrhosis (n = 338), and with decompensated cirrhosis (n = 251).
  
  
  
  Baseline PRO scores were as much as 33.5% lower in patients with decompensated cirrhosis than in patients without cirrhosis (P < .05). Following treatment with ribavirin-containing regimens, changes in PRO scores were similar among patients with compensated and decompensated cirrhosis (all P > .01). Treatment with these regimens increased some PRO scores by as much as 11.8% from baseline (P < .05) and reduced others, by as much as 7.1% (P < .05). Despite this, by 12 weeks after cessation of treatment with ribavirin-containing regimens, all PRO decrements resolved; PRO scores increased by as much as 14.2%, and as much as 17.1% at 24 weeks after treatment, regardless of cirrhosis status (all P > .01 between cirrhosis groups). In contrast, treatment with ribavirin-free sofosbuvir and velpatasvir increased PRO scores for patients with compensated cirrhosis, and even more so in patients with decompensated cirrhosis starting at treatment Week 4; no statistically significant decrement was observed at any time point (all 1-sided P values > .05). In multivariate analysis, compensated cirrhosis was associated with a 2.3% to 5.0% greater increase in PRO scores following treatment with sofosbuvir and velpatasvir (P < .05); decompensated cirrhosis was associated with a 5.5%-9.1% greater increase (P < .002). Clinicaltrials.gov number, NCT02201940, NCT02220998, NCT02201953, NCT02201901.
  
  
  
  In an analysis of data from 4 phase 3 clinical trials, we found that patients with HCV infection (especially those with decompensated cirrhosis) have significant increases in their PRO scores during treatment with sofosbuvir and velpatasvir and after achieving a sustained virologic response.
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Center for Outcomes Research, Washington, District of Columbia.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
authors.affiliation: Toronto Center for Liver Disease, Toronto, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Feld
authors.affiliation: Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
authors.affiliation: Queen Mary University London, London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Intermountain Medical Center, Salt Lake City, Utah.
authors.forename: Michael
authors.initials: M
authors.lastname: Charlton
authors.affiliation: Baylor University Medical Center, Dallas, Texas.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Center for Outcomes Research, Washington, District of Columbia.
authors.forename: Fatema
authors.initials: F
authors.lastname: Nader
authors.affiliation: Center for Outcomes Research, Washington, District of Columbia.
authors.forename: Linda
authors.initials: L
authors.lastname: Henry
authors.affiliation: Center for Outcomes Research, Washington, District of Columbia.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D008103:Liver Cirrhosis; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D006576:Heterocyclic Compounds, 4 or More Rings; D012254:Ribavirin; D000069474:Sofosbuvir; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans
keywords: DAA; Direct-Acting Antivirals; PRO; Quality of Life