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.
Graphical abstract
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Centers for Disease Control and Prevention (CDC).MMWR Morb Mortal Wkly Rep. 2012; 61: 1-18
- Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement.Ann Intern Med. 2013; 159: 349-357
- Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression.Gastroenterology. 2010; 138: 513-521
- Epidemiology of viral hepatitis and hepatocellular carcinoma.Gastroenterology. 2012; 142 (e1): 1264-1273
- The portrait of an adult liver transplant recipient in the United States from 1987 to 2013.JAMA Intern Med. 2014; 174: 1407-1409
- Manifestations of chronic hepatitis C virus infection beyond the liver.Clin Gastroenterol Hepatol. 2010; 8: 1017-1029
- The impact of hepatitis C burden: an evidence-based approach.Aliment Pharmacol Ther. 2014; 39: 518-531
- Chronic hepatitis C virus (HCV) disease burden and cost in the United States.Hepatology. 2013; 57: 2164-2170
- Impact of hepatitis C on health related quality of life: a systematic review and quantitative assessment.Hepatology. 2005; 41: 790-800
- Fatigue and health-related quality of life (HRQL) in chronic hepatitis C virus infection.Dig Dis Sci. 2007; 52: 2531-2539
- Review of patient-reported outcome measures in chronic hepatitis C.Health Qual Life Outcomes. 2012; 7: 92
- Minimal impact of sofosbuvir and ribavirin on health related quality of life in chronic hepatitis C (CH-C).J Hepatol. 2014; 60: 741-747
- Effects of sofosbuvir-based treatment, with and without interferon, on outcome and productivity of patients with chronic hepatitis C.Clin Gastroenterol Hepatol. 2014; 12 (e13): 1349-1359
- The effects of HCV infection and management on health-related quality of life.Hepatology. 2007; 45: 806-816
- The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity.J Hepatol. 2001; 34: 140-147
- Interferon (IFN), Ribavirin (RBV), duration of treatment and baseline Patient-Reported Outcomes (PROs) predict adherence to the new regimens for treatment of Chronic Hepatitis C (CH-C).Hepatology. 2015; 62: 371A
- Systematic review: patient-reported outcomes in chronic hepatitis C-the impact of liver disease and new treatment regimens.Aliment Pharmacol Ther. 2015; 41 ([Epub 2015 Jan 23. Review]): 497-520https://doi.org/10.1111/apt.13090
- An in-depth analysis of patient-reported outcomes in patients with chronic hepatitis C treated with different anti-viral regimens.Am J Gastroenterol. 2016; ([Epub ahead of print])https://doi.org/10.1038/ajg.2016.99
- Sofosbuvir and ribavirin in HCV genotypes 2 and 3.N Engl J Med. 2014; 370: 1993-2001
- ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection.Gastroenterology. 2014; 147 (PEARL II): 359-365
- ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis.N Engl J Med. 2014; 370 (TURQUOISE II): 1973-1982
- Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.N Engl J Med. 2014; 370 (SAPPHIRE II): 1604-1614
- Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.Lancet. 2014; 384: 1756-1765
- Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.N Engl J Med. 2014; 370: 1889-1898
- Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med. 2014; 370: 1483-1493
- Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.N Engl J Med. 2014; 370: 1879-1888
- All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study.Hepatology. 2015; 61: 1127-1135
- Daclatasvir: A NS5A replication complex inhibitor for hepatitis C infection.Ann Pharmacother. 2016; 50: 39-46
- Effects of sofosbuvir-based treatment, with and without interferon, on outcome and productivity of patients with chronic hepatitis C.Clin Gastroenterol Hepatol. 2014; 12 (e13): 1349-1359
- Patient-reported outcomes assessment in chronic hepatitis C treated with sofosbuvir and ribavirin: the VALENCE study.J Hepatol. 2014; 61: 228-234
- Patient-reported outcomes in chronic hepatitis C patients with cirrhosis treated with sofosbuvir-containing regimens.Hepatology. 2014; 59: 2161-2169
- Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir.J Hepatol. 2015; 63: 337-345
- The impact of ledipasvir/sofosbuvir on patient-reported outcomes in cirrhotic patients with chronic hepatitis C: the SIRIUS study.Liver Int. 2016; 36: 42-48
- Sofosbuvir and ribavirin for treatment of chronic hepatitis C in patients coinfected with hepatitis C virus and HIV: the impact on patient-reported outcomes.J Infect Dis. 2015; 212: 367-377
- Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: results from the ION-1, -2, and -3 clinical trials.Hepatology. 2015; 61: 1798-1808
- The patient’s journey with chronic hepatitis C from interferon plus ribavirin to interferon- and ribavirin-free regimens: a study of health-related quality of life.Aliment Pharmacol Ther. 2015; 42: 286-295
- Health-related quality of life in genotype 1 treatment-naïve chronic hepatitis C patients receiving telaprevir combination treatment in the ADVANCE study.Aliment Pharmacol Ther. 2013; 38: 124-133
- Work productivity among treatment-naïve patients with genotype 1 chronic hepatitis C infection receiving telaprevir combination treatment.J Viral Hepat. 2015; 22: 8-17
- Systematic review: patient-reported outcomes in chronic hepatitis C–the impact of liver disease and new treatment regimens.Aliment Pharmacol Ther. 2015; 41: 497-520
- Determining whether a patient is feeling better: pitfalls from the science of human perception.J Gen Intern Med. 2011; 26: 900-906
- Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection.N Engl J Med. 2015; 373: 2599-2607
- Interpreting SF-36 summary health measures: a response.Qual Life Res. 2001; 10: 405-413
- The Functional Assessment of Chronic Illness Therapy (FACIT) measurement system: validation of version 4 of the core questionnaire.Qual Life Res. 1999; 8: 604
- Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease.Gut. 1999; 45: 295-300
- The validity and reproducibility of a work productivity and activity impairment instrument.Pharmacoeconomics. 1993; 4: 353-365
- Effects of viral eradication with ledipasvir and sofosbuvir, with or without ribavirin, on measures of fatigue in patients with chronic hepatitis C virus infection.Clin Gastroenterol Hepatol. 2016; 14 (e3): 156-164
- Hepatitis C virus-associated neurocognitive and neuropsychiatric disorders: advances in 2015.World J Gastroenterol. 2015; 21: 11974-11983
- Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition.J Hepatol. 2012; 56: 549-556
- A methodology for successfully producing global translations of patient reported outcome measures for use in multiple countries.Value Health. 2010; 13: 128-131
Article info
Publication history
Published online: March 05, 2016
Accepted:
February 22,
2016
Received in revised form:
February 10,
2016
Received:
December 15,
2015
Identification
Copyright
© 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
