Sofosbuvir and ribavirin in adolescents 12‐17 years old with hepatitis C virus genotype 2 or 3 infection

Wirth, Stéfan; Rosenthal, Philip; González‐Peralta, Regino P.; Jonas, Maureen M.; Balistreri, William F.; Lin, Chen‐Chou; Hardikar, Winita; Kersey, Kathryn; Massetto, Benedetta; Kanwar, Bittoo; Brainard, Diana M.; Shao, Jiang; Svarovskaia, Evguenia S.; Kirby, Brian J.; Arnon, Ronen; Murray, Karen F.; Schwarz, Kathleen B.

doi:10.1002/hep.29278

Cited by 99 publications

(100 citation statements)

References 23 publications

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“…In clinical trials,26, 27 adult formulations of both sofosbuvir‐based regimens had plasma exposures in adolescent patients that were comparable to those in adults, with no severe AEs or laboratory abnormalities. In adolescents with GT1 infection and treated for 12 weeks with sofosbuvir plus ledipasvir, the SVR12 rate was 98% 26.…”

Section: Discussionmentioning

confidence: 95%

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: Discussionmentioning

confidence: 95%

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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“…Studies implementing DAA regimens in adolescents and children have thus far been limited . They were preceded by a few individual case reports that documented successful treatment of HCV in young patients, namely with sofosbuvir/ledipasvir dual therapy …”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of combined sofosbuvir/daclatasvir treatment of children and adolescents with chronic hepatitis C Genotype 4

Ghaffar

Naghi

Gawad

et al. 2018

Journal of Viral Hepatitis

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Summary Direct‐acting antivirals have become available for treating chronic HCV (hepatitis C virus) infection in adults and, recently, in children at least 12 years old. Our aim was to investigate the safety and efficacy of combined sofosbuvir (SOF)/daclatasvir (DCV) for HCV Genotype 4 in children aged 8 to 18 years or weighing 17 kg or more. A total of 40 chronic HCV‐infected, treatment‐naïve children with well compensated livers were recruited from two sites. Patients received combined therapy of SOF (400 mg/d for patients weighing greater than 45 kg; 200 mg/d for patients weighing 17 to 45 kg) and DCV (60 mg/d for patients weighing greater than 45 kg; 30 mg/d for patients weighing 17 to 45 kg) for 12 weeks. They were followed up regularly by clinical examination and laboratory tests during treatment (weekly in the first month then monthly to the end of treatment), every 3 months for 6 months post‐treatment, and at 48 weeks post‐treatment. In our cohort, which included 45% of children below the age of 12 years (72.5% genotype 4 and 27.5% mixed genotype 4 and 1), end of treatment response (ETR) was 97.5%. Sustained virologic response for weeks 12 and 24 post‐treatment (SVR12 and SVR24) were 97.5% and 95%, respectively, on an intention to treat basis, and 100% and 100% for those who completed the study protocol. Observed side effects were mild and none required drug cessation. Combined SOF/DCV was found to be effective and safe for treating HCV Genotype 4‐infected children, 8 years of age and above.

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“…Data from a Phase II, multicenter, open-label study (NCT 02175758) evaluating safety and efficacy of SOF with ribavirin in 52 patients aged 12–17 years (median age 15 years) with CHC with genotype 2 or 3 also showed promising results 52. Thirteen patients genotype 2 (25%) and 39 with genotype 3 (75%) infection were recruited from 30 study sites in Australia, Germany, Italy, New Zealand, Russia, the UK, and the US.…”

Section: Other Published Daa Data In Adolescentsmentioning

confidence: 99%

“…No patients had known cirrhosis; 21/52 (40%) were documented as not having cirrhosis, and the remainder were not assessed for presence or absence of cirrhosis. All received SOF 400 mg once daily, and weight-based ribavirin (15 mg/kg divided into two doses), either for 12 weeks (genotype 2) or 24 weeks (genotype 3) 52. The adult dose of SOF 400 mg was given as pharmacokinetic results showed similar plasma exposure and safety profiles 53.…”

Section: Other Published Daa Data In Adolescentsmentioning

confidence: 99%

“…The most common adverse events were nausea (27%) and headache (23%), and no patients discontinued treatment due to adverse events. Only one patient reported a grade 3 (severe) adverse event, which was a shoulder joint injury that was not considered related to the study drug 52. The study is ongoing in younger children.…”

Section: Other Published Daa Data In Adolescentsmentioning

confidence: 99%

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Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C

Yang

Goel

Ahmed

2018

AHMT

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Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%–2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

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Sofosbuvir and ribavirin in adolescents 12‐17 years old with hepatitis C virus genotype 2 or 3 infection

Abstract: Sofosbuvir and ribavirin was safe and highly effective in adolescents with chronic hepatitis C virus genotype 2 or 3 infection. (Hepatology 2017;66:1102-1110).

Cited by 99 publications

References 23 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

Safety and efficacy of combined sofosbuvir/daclatasvir treatment of children and adolescents with chronic hepatitis C Genotype 4

Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C

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