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Biological therapeutic drug monitoring: a step towards precision medicine?
  1. William D Renton1,
  2. Athimalaipet V Ramanan2
  1. 1 Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  2. 2 Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  1. Correspondence to Professor Athimalaipet V Ramanan, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1TH, UK; avramanan{at}hotmail.com

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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 trigger an RES response may slow down biological elimination by acting as a depot for the protein.1

Like most medications, there is a clear correlation between biological medication serum concentrations and therapeutic effect. Therapeutic trough concentrations have been established among adult patients using anti-TNF-α biologics for a range of different diseases. Adalimumab trough concentrations of 5–8 µg/mL are sufficient to achieve an adequate clinical response in adults with rheumatoid arthritis (RA), with higher concentrations providing no additional benefit.2 Similar adalimumab trough concentrations provide optimal effect …

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