Hepatitis B in children is of particular concern, as the younger a person is when she/he contracts HBV, the greater likelihood of developing the chronic form of the disease. While HBV vaccination (primarily of users of IV drugs, or of infants born to HBV+ mothers) remains the greatest HBV-related public health challenge for Canada, we also should consider the importance of treatment to our youngest victims of HBV. While this could involve a greater investment in research and the cost of care, if we must justify this from a pharmacoeconomic perspective, preventing future liver damage in one HBV+ young person will pay off in many more “Quality-Adjusted Life Years” than treating dozens of their HBV+ elders.
Pre-natal monitoring and care of mothers and post-natal immunizations and monitoring of infants are critical in preventing HBV exposure. However, some children are still, nevertheless, contracting this disease in Canada (or coming here as young immigrants previously exposed); giving them the best treatment available, as early as possible, is obviously of paramount importance to their future health. Here is the latest information we could find on this.
The big news was that in December of 2018 the USA’s FDA revised the drug label for Viread (TDF [or] tenofovir disoproxil fumarate, produced by Gilead Sciences) to include use of the drug for children ages 2 through 11 (https://www.healio.com/hepatology/chronic-hepatitis/news/online/%7Bb1bf2a48-ead6-4486-9ed8-bd93c9a501bb%7D/viread-label-revision-includes-pediatric-patients-with-chronic-hbv). The FDA had previously indicated use of Viread for children 12 through 17. Positive results of recent trials with those aged 2-11 led to the FDA’s decision. For example, after 48 weeks, 77% of participants had a viral load less than 400 (compared to 7% of the control group). Also, 66% of participants reached normalization in their ALT scores (only 15% of the control group did this).
However, as the trials were against placebos, it is unclear how Viread compared with other HBV treatments. Also, Viread is known to have negative impact on bone density; as expected, those on placebo gained more bone mineral density than did those on Viread. Long-term bone health or fracture risks for children have not yet been determined. As for viral resistance, 15 children who had been on Viread ended the trials with a viral load above 400. Of these, 14 showed no evidence of viral resistance to Viread, but we wonder about the one child who may have. Finally, the use of a newer medication, Vemlidy (TAF [or] tenofovir alafenamide, also produced by Gilead) which seems to have less impact on bone density, may be of greater long-term benefit to children than Viread. Many questions seem to remain for further research into the use of either Viread or Vemlidy for hepatitis B in children.
And…what about treating kids with chronic hepatitis B in Canada? While CADTH has approved both medications’ use in Canada, the substantially higher cost of Vemlidy has discouraged provincial PharmaCares from covering it. Note that both medications are also used for HIV, so HIV studies are often used to determine safety and efficacy. Currently Canada’s drug labels for the two HBV treatments read as follows:
VIREAD (TDF): “The safety and efficacy of VIREAD in adolescent patients aged 12 to <18 years is supported by data from one randomized study in which VIREAD was administered to HIV-1 infected treatment experienced subjects. In this study, the pharmacokinetic profile of VIREAD was similar to that found to be safe and effective in adult populations…Safety and efficacy in pediatric patients less than 12 years of age have not been established.”
“In a clinical study of HIV-1 infected adolescent subjects (Study 321), bone effects were similar to adult subjects. Under normal circumstances, BMD [bone mineral density] increases rapidly in adolescents. In this study, the mean rate of bone gain was less in the VIREAD-treated group compared to the placebo group. Six VIREAD treated adolescents and one placebo treated adolescent had significant (>4%) lumbar spine BMD loss in 48 weeks. Among 28 subjects receiving 96 weeks of VIREAD, Z-scores declined by −0.341 for lumbar spine and −0.458 for total body. Skeletal growth (height) appeared to be unaffected. Markers of bone turnover in VIREAD-treated adolescents increased bone turnover, consistent with the effects observed in adults. The effects of VIREAD-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown.”
VEMLIDY (TAF): “Safety and effectiveness of VEMLIDY in pediatric patients less than 18 years of age have not been established.” (http://www.gilead.ca/application/files/9715/3756/6953/Vemlidy_English_PM_e193066-GS-001.pdf)