Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from ASTRAL-1 placebo-controlled trial

Background & Aims: The new pan-genotypic regimen [sofosbuvir (SOF) and velpatasvir (VEL)] for hepatitis C virus (HCV) has been associated with high efficacy. The aim of this study was to assess patient-reported outcomes (PROs) of this regimen. Methods: The PRO data (CLDQ-HCV, SF-36, FACIT-F, WPAI) came from the ASTRAL-1 study, a multicenter multinational blinded placebo-controlled phase 3 clinical trial of a fixed dose combination of SOF 400 mg and VEL 100 mg for patients with genotype 1, 2, 4, 5, and 6 compared to placebo for 12 weeks. Results: 624 patients received active treatment [618 achieved sustained virologic response (SVR)], and 116 received placebo. The baseline PRO scores were similar. By treatment week 4, patients receiving SOF/VEL experienced improvements in general health (on average, +2.3 points), emotional well-being (+3.4), FACIT-F (+1.3), and all domains of CLDQ-HCV (+2.1 to +7.3) (all p < 0.005). On the other hand, the only PRO that improved in patients receiving placebo was the worry domain of CLDQ- HCV: +4.6 (p = 0.002). By the end of treatment, improvement in PRO scores with SOF/VEL continued, and no improvement was noted in the placebo. Improvement in PROs were also noted 12 and 24 weeks post-treatment: +3.7, on average, in patients with SVR-12 after SOF/VEL vs. -2.6, on average, in the placebo arm (p < 0.005). Multivariate analysis showed that treatment-emergent changes in PROs were predicted by receiving SOF/VEL for some summary PRO score (p < 0.005). Conclusions: This placebo-controlled trial shows that patients treated with SOF/VEL experience significant improvement of their PROs during treatment and after achieving SVR. Lay summary: In patients with chronic hepatitis C infection, health-related quality of life and work productivity are often impaired due to HCV-related fatigue. Treatment of hepatitis C with interferon-based regimens, which was the standard of care for all HCV patients until recently, had substantial and potentially debilitating side effects. These regimens caused additional impairment in health-related quality of life and work productivity during treatment and shortly after treatment cessation. The newly developed interferon-free combination of sofosbuvir and velpatasvir has been shown to improve health-related quality of life during treatment, and lead to an improvement in a number of indicators of patient-reported outcomes after successful clearance of HCV and achieving sustained virologic response. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.