Summary of the consortium
For more than a decade, clinicians have been using a growing number of monoclonal antibodies and related molecules (Fc fusion protein, pegylated Fab). These compounds have radically transformed the practice of clinicians, most notably for patients with inflammatory conditions such as rheumatoid arthritis, Crohn’s disease and multiple sclerosis.
Considerable inter-individual variability in the clinical response, in particular to TNF-antagonists, has been documented and researchers are seeking to explain this variability. It has been shown that pharmacokinetics (drug concentration versus time) is highly variable between patients and is related to clinical response, patients with high concentrations of the drug being more likely to respond than those who have low concentrations. Pharmacokinetic and pharmacokinetic-pharmacodynamic (PK-PD) modelling allows a description of the dose-response relationship to identify the sources of inter-individual variability, for both PK and PD-PD relationship.
Over the last few years, academic groups have developed tools to monitor the pharmacological effect of therapeutic antibodies by means of measuring trough concentrations. This practice called therapeutic drug monitoring (TDM), involves the measurement in sera of the concentration of the drug, often in combination with anti-drug antibodies (ADA) detection on the one hand, and the disease activity of patients on the other hand. TDM may help clinician to adjust the dose regimen according to individual characteristics to improve clinical outcomes and avoid adverse events related to unnecessary overexposure. However, although TDM of biopharmaceuticals seems promising, its implementation into clinical setting deserves further research to develop reliable and standardized assays, mathematical modelling (population approaches to analyze databases, mechanistic PK-PD modelling, clinical trial simulation) and clinical expertise.
The partners of the MAGE (Monitoring of Antibodies academic Group in Europe) have an experience in clinical research on monoclonal antibodies and develop their research in academic laboratories. Given a strong expertise in pharmacology, immunology, and applied mathematics, the MAGE is gathering increasing scientific evidence to support a therapeutic drug monitoring of these particular molecules in the field of inflammatory diseases.
The aims of the MAGE consortium are
- to write position papers and original manuscript in collaboration;
- to standardize assays for drug measurement,
- to perform analyses in partnership to develop algorithms for TDM and
- to design comparative effectiveness clinical trials to validate these tools.