Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin

Feld, Jordan J., Kowdley, Kris V., Coakley, Eoin, Sigal, Samuel, Nelson, David R., Crawford, Darrell, Weiland, Ola, Aguilar, Humberto, Xiong, Junyuan, Pilot-Matias, Tami, DaSilva-Tillmann, Barbara, Larsen, Lois, Podsadecki, Thomas and Bernstein, Barry (2014) Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. New England Journal of Medicine, 370 17: 1594-1603. doi:10.1056/NEJMoa1315722

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Author Feld, Jordan J.
Kowdley, Kris V.
Coakley, Eoin
Sigal, Samuel
Nelson, David R.
Crawford, Darrell
Weiland, Ola
Aguilar, Humberto
Xiong, Junyuan
Pilot-Matias, Tami
DaSilva-Tillmann, Barbara
Larsen, Lois
Podsadecki, Thomas
Bernstein, Barry
Title Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 1533-4406
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1056/NEJMoa1315722
Open Access Status File (Publisher version)
Volume 370
Issue 17
Start page 1594
End page 1603
Total pages 10
Place of publication Boston, MA, United States
Publisher Massachussetts Medical Society
Language eng
Formatted abstract
BACKGROUND: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the non-nucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.

METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), and dasabuvir (250 mg twice daily) with ribavirin (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78%) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B.

RESULTS: A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A. The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6% in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B.

CONCLUSIONS: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.  
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Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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