Zobair M Younossi1,2, Maria Stepanova1,2, Stanislas Pol3, Jean-Pierre Bronowicki4, Maria Patrizia Carrieri5,6,7, Marc Bourlière8. 1. Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA. 2. Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA. 3. Department of Hepatology, Hôpital Cochin et Université Paris-René Descartes, Paris, France. 4. CHU de Nancy-Hôpital Brabois Adulte, Vandoeuvre-lès-Nancy, France. 5. INSERM, UMR912 (SESSTIM), Marseille, France. 6. UMR_S912, IRD, Aix Marseille Université, Marseille, France. 7. ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France. 8. Hôpital Saint Joseph, Marseilles, France.
Abstract
BACKGROUND:Interferon- and ribavirin (RBV)-free regimens can improve patient-reported outcomes (PROs) during treatment. AIM: To compare PROs during treatment with ledipasvir and sofosbuvir (LDV/SOF) to placebo and to LDV/SOF + RBV. METHODS:Treatment-experienced CH-C genotype 1 patients with compensated cirrhosis (N = 154) were randomized to receive 24 weeks of LDV/SOF or 12 weeks of placebo followed by 12 weeks of LDV/SOF + RBV (the SIRIUS clinical trial). While blinded to their HCV RNA level and study treatment, patients completed PRO questionnaires (SF-36, FACIT-F, CLDQ-HCV, WPAI:SHP) at baseline, during and post-treatment. RESULTS:Baseline PRO scores were similar between the two study arms. Patients receiving LDV/SOF showed improvement in a number of PROs (predominantly related to mental health) starting as early as 4 weeks after treatment initiation; no PRO decrement from baseline were noted, and no PRO scores were inferior to placebo (all P > 0.05). In the second 12 weeks, patients who were receiving LDV/SOF continued to improve PROs (up to +9.2% from a 100% maximum possible score, P < 0.05), while patients receiving LDV/SOF + RBV had less gains or no improvement in their PRO scores. However, regardless of the regimen, patients who successfully cleared the virus (N = 149) had significant improvement in all aspects of PROs (up to +12.2% by post-treatment week 12, up to +16.9% by week 24). CONCLUSIONS: Treatment-experienced cirrhotic patients experience a notable improvement of their PROs during treatment with LDV/SOF. Furthermore, achieving SVR-12 is associated with significant PRO improvement, which further improves at post-treatment week 24 in this difficult to treat group of patients with chronic hepatitis C.
RCT Entities:
BACKGROUND: Interferon- and ribavirin (RBV)-free regimens can improve patient-reported outcomes (PROs) during treatment. AIM: To compare PROs during treatment with ledipasvir and sofosbuvir (LDV/SOF) to placebo and to LDV/SOF + RBV. METHODS: Treatment-experienced CH-C genotype 1 patients with compensated cirrhosis (N = 154) were randomized to receive 24 weeks of LDV/SOF or 12 weeks of placebo followed by 12 weeks of LDV/SOF + RBV (the SIRIUS clinical trial). While blinded to their HCV RNA level and study treatment, patients completed PRO questionnaires (SF-36, FACIT-F, CLDQ-HCV, WPAI:SHP) at baseline, during and post-treatment. RESULTS: Baseline PRO scores were similar between the two study arms. Patients receiving LDV/SOF showed improvement in a number of PROs (predominantly related to mental health) starting as early as 4 weeks after treatment initiation; no PRO decrement from baseline were noted, and no PRO scores were inferior to placebo (all P > 0.05). In the second 12 weeks, patients who were receiving LDV/SOF continued to improve PROs (up to +9.2% from a 100% maximum possible score, P < 0.05), while patients receiving LDV/SOF + RBV had less gains or no improvement in their PRO scores. However, regardless of the regimen, patients who successfully cleared the virus (N = 149) had significant improvement in all aspects of PROs (up to +12.2% by post-treatment week 12, up to +16.9% by week 24). CONCLUSIONS: Treatment-experienced cirrhotic patients experience a notable improvement of their PROs during treatment with LDV/SOF. Furthermore, achieving SVR-12 is associated with significant PRO improvement, which further improves at post-treatment week 24 in this difficult to treat group of patients with chronic hepatitis C.
Authors: Zobair M Younossi; Maria Stepanova; Mark Sulkowski; Graham R Foster; Nancy Reau; Alessandra Mangia; Keyur Patel; Norbert Bräu; Stuart K Roberts; Nezam Afdhal; Fatema Nader; Linda Henry; Sharon Hunt Journal: Clin Infect Dis Date: 2016-07-20 Impact factor: 9.079