Biological therapeutic drug monitoring: a step towards precision medicine?

Biological medications including monoclonal antibodies against tumour necrosis factor-α (TNF-α), such as infliximab and adalimumab, have revolutionised the treatment of children and young people with autoimmune conditions such as inflammatory bowel disease, juvenile idiopathic arthritis (JIA) and childhood chronic inflammatory uveitis. Emerging evidence is increasingly supporting the use of therapeutic drug monitoring (TDM) to help optimise biological efficacy, safety and cost-effectiveness.

The pharmacokinetics of biologics is complex and in contrast to traditional medications; predominantly due to their large molecular size and structural complexity, they do not undergo hepatic metabolisation and are instead broken down by intracellular lysosomal proteolytic degradation. Also, unlike traditional medications, they have immunogenic potential and the formation of antidrug antibodies (ADA) can significantly affect their pharmacokinetic profile. ADA directed against the corresponding biologic can trigger proteolytic elimination in the reticuloendothelial system (RES) leading to increased clearance of these molecules. Conversely, an immune complex that does not...

from Archives of Disease in Childhood current issue http://bit.ly/2NdCPAw