ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis.

By F. Poordad, C. Hézode, R. Trinh, Kris V. Kowdley, S. Zeuzem, K. Agarwal, M. Shiffman, H. Wedemeyer, T. Berg, E. Yoshida and 7 more. New England Journal of Medicine, 2014

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BACKGROUND Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis. METHODS We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive either 12 or 24 weeks of treatment with ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. The rate of sustained virologic response in each group was compared with the estimated rate with a telaprevir-based regimen (47%; 95% confidence interval [CI], 41 to 54). A noninferiority margin of 10.5 percentage points established 43% as the noninferiority threshold; the superiority threshold was 54%. RESULTS A total of 191 of 208 patients who received 12 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 91.8% (97.5% CI, 87.6 to 96.1). A total of 165 of 172 patients who received 24 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 95.9% (97.5% CI, 92.6 to 99.3). These rates were superior to the historical control rate. The three most common adverse events were fatigue (in 32.7% of patients in the 12-week group and 46.5% of patients in the 24-week group), headache (in 27.9% and 30.8%, respectively), and nausea (in 17.8% and 20.3%, respectively). The hemoglobin level was less than 10 g per deciliter in 7.2% and 11.0% of patients in the respective groups. Overall, 2.1% of patients discontinued treatment owing to adverse events. CONCLUSIONS In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1 infection and cirrhosis, multitargeted therapy with the use of three new antiviral agents and ribavirin resulted in high rates of sustained virologic response. Drug discontinuations due to adverse events were infrequent. (Funded by AbbVie; TURQUOISE-II ClinicalTrials.gov number, NCT01704755.).

Subfields: Epidemiology, Hepatology, Infectious Diseases

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Citations in the corpus

Hepatitis C guidance: AASLD‐IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus (2015, background): “For those with cirrhosis in whom a prior PEG-IFN–based regimen has failed, the recommendations for treatment are the same as those for genotype 1a patients with cirrhosis, except the treatment duration of PrOD can be reduced to 12 weeks and RBV can be omitted.(71) 938 AASLD/IDSA HCV GUIDANCE PANEL H”
EASL Recommendations on Treatment of Hepatitis C 2015. (2015, background): “Data on the efficacy and safety of the combination of ritonavir-boosted paritaprevir, ombitasvir and dasabuvir with ribavirin in compensated cirrhotic patients infected with genotype 1 have been published [45].”
EASL Clinical Practice Guidelines: Liver transplantation. (2016, background): “Data on the efficacy and safety of the combination of ritonavir-boosted paritaprevir, ombitasvir and dasabuvir with RBV in compensated cirrhotic patients infected with genotype 1 have shown SVR12 rates around 95% [37], with slightly lower efficacy (around 85–90%) in those individuals with lower plat”
Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection (2017, methodology): “We identified 1 study with low risk of bias that used the two-DAA regimen without dasabuvir (45) and 9 studies (5 with low risk of bias and 4 with moderate risk of bias) that used the three-DAA regimen for 12 or 24 weeks (12, 13, 22, 23, 37, 38, 40, 41).”