Biologics in pediatric rheumatology Towards personalized medicine

Since the introduction of biologics, treatment options for children with rheumatic diseases have increased, and their outcome has improved enormously. However, finding the best treatment strategy can sometimes be a quest, partly because it is unknown which drug works best for the individual patient or which side effects will occur. This thesis, aims to gain more knowledge about personalizing treatment with biologics for children with rheumatic diseases.
The first part of this thesis focusses on the treatment of children with Juvenile Idiopathic Arthritis (JIA). We provided an overview of children with JIA treated with anti-TNF drugs at the Amsterdam UMC, where drug concentrations and anti-drug antibodies (ADAs) in the blood were measured and concluded that therapeutic drug monitoring in anti-TNF treatment may be valuable in making personalized treatment decisions in JIA. We analyzed pharmacokinetic data in this patient population and described the development of a pharmacokinetic model specific for children with JIA for infliximab and for adalimumab.
In the second part, the focus was on children with systemic autoimmune diseases treated with rituximab. An overview of pharmacokinetics and pharmacodynamics of rituximab in children with various systemic autoimmune diseases was presented, focusing on rituximab levels in blood, presence of rituximab ADAs, B cell depletion and time to repopulation and anaphylactic reactions. We reported the frequency and severity of infections after rituximab and studied the association with immunoglobulin levels. Distribution of B cell subsets in the peripheral blood of these children was described before rituximab treatment and after B cell repopulation.