ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis

Poordad, Fred; Hézode, Christophe; Trinh, Roger; Kowdley, Kris V.; Zeuzem, Stefan; Agarwal, Kosh; Shiffman, Mitchell L.; Wedemeyer, Heiner; Berg, Thomas; Yoshida, Eric M.; Forns, Xavier; Lovell, Sandra; Silva-Tillmann, Barbara Da; Collins, Christine A.; Campbell, Andrew; Podsadecki, Thomas; Bernstein, Barry

doi:10.1056/nejmoa1402869

Cited by 816 publications

(771 citation statements)

References 25 publications

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“…This safety profile is consistent with that reported in previous studies in adult patients treated with these drug regimens,18, 19, 20, 21, 22, 23 suggesting that the adult regimen is suitable for treating adolescents without the need for additional clinical monitoring or dose adjustment.…”

Section: Discussionsupporting

confidence: 91%

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Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4

Leung

Wirth

Yao

et al. 2018

Hepatology Communications

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In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open‐label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12‐17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty‐eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12‐17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%‐100%). No treatment‐emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.

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Section: Discussionsupporting

confidence: 91%

“…These all‐oral, IFN‐free, multitargeted regimens have shown high SVR12 rates and good tolerability in phase 3 studies for a broad range of adult patients infected with GT1 or GT4 18, 19, 20, 21, 22, 23. However, these regimens have not been studied in children or adolescents.…”

mentioning

confidence: 99%

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4

Leung

Wirth

Yao

et al. 2018

Hepatology Communications

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“…Overall, the frequency and clinical severity of anaemia were low across the six trials; 6.5% of subjects had a decrease in haemoglobin levels to <10 g/dL during treatment with OBV/PTV/r + DSV + RBV, and <1% had a haemoglobin decrease to <8 g/dL 8, 11, 12, 13, 14…”

Section: Introductionmentioning

confidence: 95%

“…Six phase 3 trials evaluated the all‐oral DAA regimen of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor identified by AbbVie and Enanta, and dosed with ritonavir, PTV/r) and dasabuvir (DSV, a non‐nucleoside NS5B RNA polymerase inhibitor) with or without RBV in HCV genotype (GT)1‐infected patients that were either treatment naive or pegIFN experienced, with or without compensated cirrhosis 8, 11, 12, 13, 14. Overall, the frequency and clinical severity of anaemia were low across the six trials; 6.5% of subjects had a decrease in haemoglobin levels to <10 g/dL during treatment with OBV/PTV/r + DSV + RBV, and <1% had a haemoglobin decrease to <8 g/dL 8, 11, 12, 13, 14…”

Section: Introductionmentioning

confidence: 99%

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

Feld

Bernstein

Younes

et al. 2018

Liver International

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Background & AimsSome individuals with hepatitis C virus infection treated with direct‐acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus‐infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.MethodsWe performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.ResultsOf 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post‐treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).ConclusionsRibavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post‐treatment. Patients with low baseline haemoglobin should be monitored for on‐treatment anaemia.

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“…Ever‐evolving treatment regimens are available that reliably achieve a >95% “real‐world” cure rate for all HCV genotypes 6. Efficacy has also been demonstrated in historically difficult to treat populations, such as patients with pretreatment cirrhosis, renal disease, patients previously exposed to antiviral therapy, prior null responders, those with HIV co‐infection, and patients following liver transplantation 95, 96, 97, 98, 99…”

Section: Managementmentioning

confidence: 99%

Hepatitis C virus infection in children and adolescents

Squires

Balistreri

2017

Hepatology Communications

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ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis

Cited by 816 publications

References 25 publications

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4

Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

Hepatitis C virus infection in children and adolescents

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