Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir with low-dose ribavirin in patients with chronic hepatitis C virus genotype 1a infection without cirrhosis
Fred Poordad, Shahriar Sedghi, Paul J Pockros, Natarajan Ravendhran, Robert Reindollar, Michael R Lucey, Michael Epstein, Leslie Bank, David Bernstein, Roger Trinh, Preethi Krishnan, Akshanth R Polepally, Kristina Unnebrink, Marisol Martinez, David R Nelson, Fred Poordad, Shahriar Sedghi, Paul J Pockros, Natarajan Ravendhran, Robert Reindollar, Michael R Lucey, Michael Epstein, Leslie Bank, David Bernstein, Roger Trinh, Preethi Krishnan, Akshanth R Polepally, Kristina Unnebrink, Marisol Martinez, David R Nelson
Abstract
Patients infected with hepatitis C virus (HCV) treated with interferon-free direct-acting antivirals may still require ribavirin. However, ribavirin is associated with adverse events that can limit its use. This open-label, multicentre, Phase 3 study evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir + dasabuvir (OBV/PTV/r + DSV) with low-dose ribavirin for 12 weeks in genotype 1a-infected patients without cirrhosis. The primary efficacy endpoint was sustained virologic response at post-treatment Week 12 (SVR12). The primary safety endpoint was haemoglobin <10 g/dL during treatment and decreased from baseline. Overall, 105 patients enrolled. The SVR12 rate was 89.5% (n/N = 94/105; 95% CI, 83.7-95.4). The study did not achieve noninferiority versus the historic SVR12 rate for OBV/PTV/r + DSV plus weight-based ribavirin. Five patients experienced virologic failure, four discontinued, and two had missing SVR12 data. Excluding nonvirologic failures, the SVR12 rate was 94.9% (n/N = 94/99). One patient met the primary safety endpoint. OBV/PTV/r + DSV plus low-dose ribavirin offers an alternative option for patients in whom full-dose ribavirin may compromise tolerability, although noninferiority to the weight-based ribavirin regimen was not met.
Trial registration: ClinicalTrials.gov NCT02609659.
Keywords: GEODE-II; genotype 1a; hepatitis C virus; interferon-free therapy; low-dose ribavirin.
Conflict of interest statement
F Poordad received grant/research support from AbbVie, Bristol‐Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals and Merck; is a consultant/advisor for AbbVie, Bristol‐Myers Squibb, Gilead Sciences and Merck. S Sedghi had nothing to disclose. P Pockros is a speaker/consultant/advisor for Gilead, AbbVie, Janssen and Bristol‐Myers Squibb; received research support from Gilead, AbbVie, Janssen, Bristol‐Myers Squibb, Merck, Conatus and Roche Molecular. N Ravendhran reported conflicts of interest for AbbVie, Gilead, Merck, Salix, Bristol‐Myers Squibb; received research support from Bristol‐Myers Squibb, Gilead, Merck and Salix. R Reindollar is an investigator in clinical trials/speaker/advisory board member for AbbVie. M Lucey received grant/research support from AbbVie, Gilead and Salix. M Epstein is a consultant for IM HealthScience; speaker for Pfizer and Salix. L Bank is a speaker for AbbVie; received research support from AbbVie, Gilead and Merck. D Bernstein is a consultant for Merck; received grant/research support from Gilead, Pharmasset, Vertex and Bristol‐Myers Squibb; speaker and teacher for Gilead. R Trinh, P Krishnan, AR Polepally, K Unnebrink and M Martinez are employees of AbbVie and may hold stock or stock options. D Nelson received grant/research support from Abbott, Bristol‐Myers Squibb, Boehringer Ingelheim, Gilead, Genentech, Merck, Bayer, Idenix, Vertex and Janssen.
© 2019 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.
References
- AASLD‐IDSA .Recommendations for testing, managing, and treating hepatitis C. . Accessed: June 19, 2018.
- Feld JJ, Jacobson IM, Sulkowski MS, Poordad F, Tatsch F, Pawlotsky JM. Ribavirin revisited in the era of direct‐acting antiviral therapy for hepatitis C virus infection. Liver Int. 2017;37(1):5–18.
- Poordad F, Lawitz E, Reddy KR, et al. Effects of ribavirin dose reduction vs erythropoietin for boceprevir‐related anemia in patients with chronic hepatitis C virus genotype 1 infection–a randomized trial. Gastroenterology. 2013;145(5):1035–1044 e1035.
- Ferenci P, Bernstein D, Lalezari J, et al. ABT‐450/r‐ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983–1992.
- Kwo PY, Mantry PS, Coakley E, et al. An interferon‐free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;371(25):2375–2382.
- Balk JM, Haenen GR, Koc OM, et al. Once‐daily dose regimen of ribavirin is interchangeable with a twice‐daily dose regimen: randomized open clinical trial. Pharmgenomics Pers Med. 2015;8:137–144.
- Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT‐450/r‐ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1594–1603.
- Poordad F, Hezode C, Trinh R, et al. ABT‐450/r‐ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370(21):1973–1982.
Source: PubMed