Highlights
- •Large real-world cohort of therapy in patients infected with HCV genotype 1.
- •Eight-week treatment with ledipasvir/sofosbuvir resulted in similar SVR rates to 12 weeks treatment.
- •Very high SVR rates were achieved, so shorter treatment can be recommended.
Background & Aims
Ledipasvir/sofosbuvir (LDV/SOF) for 8 to 24 weeks is approved for the treatment of
chronic hepatitis C virus infection (HCV). In the ION-3 study, 8 weeks of LDV/SOF
was non-inferior to 12 weeks in previously untreated genotype 1 (GT1) patients without
cirrhosis. According to the Summary of Product Characteristics (SmPC), 8-week treatment
may be considered in naïve non-cirrhotic GT1-patients. However, there are only limited
data on the effectiveness of an 8-week regimen of LDV/SOF under real-world conditions.
The aim of the present study was to characterise patients receiving 8 weeks of LDV/SOF
compared to those receiving 12 weeks of LDV/SOF, and to describe therapeutic outcomes
in routine clinical practice.
Methods
The German Hepatitis C-Registry is a large national real-world cohort that analyses
effectiveness and safety of antiviral therapies in chronic HCV. This data set is based
on 2,404 patients. Treatment with SOF/LDV (without RBV) for 8 or 12 weeks was initiated
on or before September 30, 2015.
Results
Overall, 84.6% (2,034/2,404) of the safety population (intention-to-treat-1 [ITT1])
and 98.2% (2,029/2,066) of the per protocol (PP) population achieved sustained virological
response at week 12 (SVR12). In the 8-week group, 85.1% (824/968) of ITT1 and 98.3%
(821/835) of PP patients achieved SVR12, while in the 12-week group, 85.5% (1,210/1,415)
of ITT1, and 98.1% (1,208/1,231) of PP patients achieved SVR12. When treated according
to the SmPC, 98.7% (739/749) of the patients achieved SVR12 (PP). Relapse was observed
in 9.5% (2/21) of cirrhotic patients treated for 8 weeks (PP).
Conclusions
Under real-world conditions a high proportion of eligible patients receiving 8-week
LDV/SOF treatment achieved SVR12. Relapse occurred more frequently in patients who
did not meet the selection criteria according to the SmPC.
Lay summary
In a large real-world cohort of patients mainly treated by physicians in private practice
in Germany, shorter HCV treatment (8-week) resulted in equivalent cure rates to 12-week
treatment in genotype 1 HCV-infected patients. Thus, shorter treatment can be recommended
in these patients which would substantially reduce costs of therapy.
Clinical Trial number: DRKS00009717 (German Clinical Trials Register, DRKS)
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
- 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
- EASL recommendations on treatment of hepatitis C 2015.J Hepatol. 2015; 63: 199-236
- No scientific basis to restrict 8 weeks of treatment with ledipasvir/sofosbuvir to patients with hepatitis C virus RNA <6,000,000 IU/mL.Hepatology. 2016; 63: 28-30
Curry MP, Bacon B, Dieterich D, Flamm SL, Guest L, Kowdley KV, et al. Effectiveness of 8 or 12 week LDV-SOF in Treatment-Naïve Patients with Non-Cirrhotic, Genotype 1 Hepatitis C: Real-World Experience from the TRIO Network. Poster presented at the 66th Annual Meeting of the American Association for the Study of Liver Diseases, Boston, MA, Nov 13–17 2015.
- Effectiveness of sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir regimens for treatment of patients with hepatitis C in the veterans affairs national healthcare system.Gastroenterology. 2016; 151: 457-471
- Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated of sustained virologic response.Gastroenterology. 2016; 151: 1131-1140
- Sofosbuvir and Ledipasvir for 8 weeks for the treatment of chronic hepatitis C virus infection in HCV-mono-infected and HIV-HCV co-infected individuals- Results from the German hepatitis c cohort (GECCO-01).Clin Infect Dis. 2016; 63: 1320-1324
- Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice.Aliment Pharmacol Ther. 2016; 44: 400-410
- Real world effectiveness of ledipasvir/sofosbuvir in 4365 treatment-naïve genotype 1 hepatitis C infected patients.Hepatology. 2016; 64: 405-416
- Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: A retrospective analysis of phase 3 data.Hepatology. 2016; 63: 437-444
- Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously untreated patients with hepatitis C virus genotype 1b infection without cirrhosis (GARNET): a single-arm, open-label, phase 3b trial.Lancet Gastroenterol Hepatol. 2017; 2: 494-500
Petersen J, Wursthorn K, Olah K, Lorenzen T, Plettenberg A, Unger S et al. Strong decrease of patients with advanced liver disease and more adherence problems to HCV therapy as DAA regimen enter third year of existence in Germany. Poster FRI-252 presented at The International Liver Congress 2017 of the European Association for the Study of the Liver. 2016 Apr 19–23; Barcelona, Spain.
- Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.N Engl J Med. 2015; 373: 705-713
- HCV RNA assay sensitivity impacts the management of patients treated with direct acting antivirals.Antivir Ther. 2015; 20: 177-183
- Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real-world cohort study.Hepatology. 2016; 64: 1893-1899
Article info
Publication history
Published online: November 10, 2017
Accepted:
November 3,
2017
Received in revised form:
November 2,
2017
Received:
January 5,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
