Ledipasvir Plus Sofosbuvir Safe, Effective in Children Age 6 to 12
Ledipasvir 45 mg-sofosbuvir 200 mg once daily with or without ribavirin was highly effective and safe for children age 6 to <12 years with chronic HCV genotype 1, 3, and 4 infection.
For children age 6 to 12 years with chronic hepatitis C virus (HCV) infection, ledipasvir plus sofosbuvir is well tolerated and highly effective, according to results published in Hepatology.
The study included children age 6 to <12 years who were infected with HCV and had plasma HCV RNA levels ≥104 IU/mL. Participants received ledipasvir 45mg plus sofosbuvir 200 mg as 2 fixed-dose combination tablets 22.5mg/100 mg once daily, with or without ribavirin, for 12 or 24 weeks. The primary end point was sustained virologic response 12 weeks after therapy.
A total of 92 participants were enrolled (88 of whom had HCV genotype 1 infection, 2 individuals had genotype 3, and 2 individuals had genotype 4), with a median age of 9 years. Of these participants, 97% were perinatally infected and 78% had never received treatment.
The researchers confirmed cirrhosis in 2 participants by liver biopsy while the degree of fibrosis was unknown in 55 participants.
The overall rate of sustained virologic response 12 weeks after therapy was 99% (91/92). The 1 participant who did not achieve sustained virologic response had relapse 4 weeks after completing 12 weeks of treatment.
The results indicated that the most common adverse events were headache and pyrexia. During treatment, 1 participant had 3 serious adverse events but they were not related to study treatment. These events were tooth abscess, abdominal pain, and gastroenteritis.
To confirm the appropriateness of the medication dosages, 12 participants underwent intensive pharmacokinetic sampling. The area under the concentration-time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared with values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies.
“Given the poor tolerability and the well-documented side effects of pegylated interferon, expanding treatment options for children [age] 6 to <12 [years] with chronic HCV infection to include an all-oral, [direct-acting antiviral] regimen would represent an important advancement in care in this patient population,” the researchers wrote.
Murray KE, Balistreri WF, Bansal S, et al. Safety and efficacy of ledipasvir-sofosbuvir with or without ribavirin for chronic hepatitis C in children ages 6-11. Hepatology. 2018;68:2158-2166.