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Published on: May 4, 2017
Monitoring antigen-specific biologics: current knowledge and future prospects
Maarten L Zandvliet1, Jine S van Bezooijen, Mariska A Bos
1Departments of *Hospital Pharmacy, †Dermatology, ‡Immunology, and §Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Abstract:
An increasing number of antigen-specific biologics have been introduced into clinical practice, and the ones that arrived first have already reached the end of their patented life span. Despite the use of these agents for over a decade, individualized dosing is not standard practice. Most patients are treated according to treatment protocols, with a fixed dose administered at fixed time intervals. Although the between-subject variability in the volume of distribution is small, there is a moderate to high between-subject variability in the clearance of these biologics. The formation of neutralizing antidrug antibodies (ADAs) further contributes to the variability in the pharmacokinetics and pharmacodynamics. After the development of assays to detect biologic drug serum concentrations and ADA titers, the first clinical studies in immune-mediated diseases such as rheumatology, gastroenterology, and dermatology have now shown clear concentration-effect relationships. By monitoring the serum trough concentrations of biologics, patients with high drug exposure could be identified and dose reductions in those patients may lead to improved safety and substantial cost savings. Low biologic drug serum concentrations may be due to the development of ADAs, and if these are detected, a switch to an alternative treatment is indicated. We envision a vast expansion of therapeutic drug monitoring to support the use of biologics, and we urge the International Association of Therapeutic Drug Monitoring and Clinical Toxicology to embark on initiatives to investigate the contribution of therapeutic drug monitoring to this field.
Insights
Individualized dosing of biologics is essential due to variable clearance and antidrug antibodies (ADAs). Therapeutic drug monitoring can optimize biologic therapy, improving safety and reducing costs for patients with immune-mediated diseases.
Area of Science:
- Pharmacology
- Immunology
- Clinical Therapeutics
Background:
- Antigen-specific biologics are increasingly used, but fixed dosing protocols persist despite significant inter-individual variability.
- Variability in biologic clearance and the development of neutralizing antidrug antibodies (ADAs) complicate treatment efficacy and safety.
- Established assays for drug concentrations and ADA titers now enable clinical studies correlating levels with outcomes.
Purpose of the Study:
- To highlight the need for individualized dosing strategies in biologic therapy.
- To emphasize the role of therapeutic drug monitoring (TDM) in optimizing biologic treatment.
- To advocate for the expansion of TDM in managing immune-mediated diseases.
Main Methods:
- Review of existing literature on biologic pharmacokinetics, pharmacodynamics, and ADA formation.
- Analysis of clinical studies demonstrating concentration-effect relationships for biologics.
- Discussion of the utility of monitoring serum trough concentrations and ADA titers.
Main Results:
- Clear concentration-effect relationships have been established for biologics in immune-mediated diseases.
- Monitoring serum trough concentrations can identify patients for dose reduction, enhancing safety and cost-effectiveness.
- Detection of low drug levels due to ADAs indicates a need for treatment switching.
Conclusions:
- Therapeutic drug monitoring (TDM) is crucial for optimizing biologic therapy by accounting for pharmacokinetic variability and ADA development.
- Implementing TDM can lead to improved patient outcomes, reduced adverse events, and significant healthcare cost savings.
- There is a strong call for the expansion of TDM initiatives to support the effective use of biologics in clinical practice.
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