title: Simeprevir added to peginterferon and ribavirin lessens time with fatigue, depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST-1, QUEST-2 and PROMISE studies.
abstract: The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient-reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES-D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double-blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response-guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline-Week 60, AUC60 ) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post-treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR-related AEs without adding to AE severity.
authors.affiliation: Janssen Global Services, LLC, High Wycombe, UK.
authors.forename: J
authors.initials: J
authors.lastname: Scott
authors.affiliation: Janssen Research and Development, Beerse, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Gilles
authors.affiliation: Janssen Research and Development, Raritan, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fu
authors.affiliation: Adelphi Values, Bollington, UK.
authors.forename: E
authors.initials: E
authors.lastname: Brohan
authors.affiliation: Adelphi Values, Bollington, UK.
authors.forename: C
authors.initials: C
authors.lastname: Panter
authors.affiliation: Adelphi Values, Bollington, UK.
authors.forename: R
authors.initials: R
authors.lastname: Arbuckle
authors.affiliation: Janssen Research and Development, Beerse, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Jessner
authors.affiliation: Janssen Research and Development, Beerse, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Beumont
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000453:epidemiology; D003863:Depression / Q000453:epidemiology*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005221:Fatigue / Q000453:epidemiology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D007372:Interferons / Q000008:administration & dosage* / Q000009:adverse effects; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069616:Simeprevir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D010919:Placebos; D012254:Ribavirin; D007372:Interferons; D000069616:Simeprevir
keywords: chronic hepatitis C; daily functioning; depressive symptoms; fatigue; health-related quality of life; simeprevir