Background and objective: Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, has greater severity in children versus adults. Belimumab is approved for systemic lupus erythematosus treatment in patients aged ≥ 5 years, and for active LN in adults in the European Union, China, Japan and Latin America, and patients aged ≥ 5 years in the USA. Low prevalence of paediatric active LN makes conducting a clinical study within a reasonable period unfeasible. We describe a model-based extrapolation of belimumab efficacy and pharmacokinetics from adults to children with LN to support US Food and Drug Administration approval of intravenous belimumab 10 mg/kg (administered every 4 weeks after the loading dose) in children (aged 5-17 years) with active LN.
Methods: This concept assumed that disease progression, response to belimumab, exposure-response, and the target belimumab exposure for efficacy are similar across adult and paediatric systemic lupus erythematosus and LN, evaluated against the published literature for paediatric LN and belimumab systemic lupus erythematosus and LN clinical trial data in adults and children. A two-compartmental population pharmacokinetic model, previously developed for adults with LN, was used to extrapolate belimumab pharmacokinetics to children with LN.
Results: The model captured the dependence of time-varying proteinuria on belimumab clearance, and therefore exposure. Sufficient target exposures for efficacy were achieved in children with active LN. A small proportion of children aged 5-11 years are predicted to have exposures below adult levels but no impact to efficacy is expected.
Conclusions: Our model demonstrated that intravenous belimumab 10 mg/kg every 4 weeks is appropriate for children aged 5-17 years with active LN.
Lupus nephritis is a serious illness of the kidneys that can develop in patients with systemic lupus erythematosus. Lupus nephritis can be especially serious in children. Belimumab is a medication often used to treat adults and children with systemic lupus erythematosus, and adults with lupus nephritis. As a result of our study, it is now also used to treat children with lupus nephritis in the USA.Belimumab was first tested in lupus nephritis clinical trials in adults, but not in children. This is because lupus nephritis is rare in children, and it would take too long to find enough patients for a trial. Instead, we used information from scientific articles and clinical trials in adults and children with lupus nephritis. As lupus nephritis affects adults and children similarly, we used a mathematical model to test if the belimumab dose used in adults could also treat lupus nephritis in children who are aged between 5 and 17 years.To test this, we assumed that adults and children react to the same dose of belimumab in a similar way. The dose we looked at was 10 mg of belimumab for every 1 kg of patient’s body weight (10 mg/kg), which is given each month via the veins. Our model also looked at how belimumab moves through the body and how this illness affects kidneys. We found that the belimumab dose scheme we looked at (10 mg/kg/month) can be used to treat children with lupus nephritis.
© 2024. The Author(s).