Individualized Dosing of Therapeutic Monoclonal Antibodies—a Changing Treatment Paradigm?

• Published in: The AAPS journal Vol. 20; no. 6; p. 99
• Main Authors: Strik, Anne S., Wang, Yow-Ming C., Ruff, Laura E., Yashar, William, Messmer, Bradley T., Mould, Diane R.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 05.09.2018
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Pharmacology/Toxicology; Pharmacy; Review Article; point of care; dashboard; inflammatory bowel disease; therapeutic drug monitoring; monoclonal antibodies
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-018-0257-y

The introduction of monoclonal antibodies (mAbs) to the treatment of inflammatory bowel disease (IBD) was an important medical milestone. MAbs have been demonstrated as safe and efficacious treatments of IBD. However, a large percentage of patients either fail to respond initially or lose response to therapy after a period of treatment. Although there are factors associated with poor treatment outcomes in IBD, one cause for treatment failure may be low mAb exposure. Consequently, gastroenterologists have begun using therapeutic drug monitoring (TDM) to guide dose adjustment. However, while beneficial, TDM does not provide sufficient information to effectively adjust doses. The pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs are complex, with numerous factors impacting on mAb PK and PD. The concept of dashboard-guided dosing based on Bayesian PK models allows physicians to combine TDM with factors influencing mAb PK to individualize therapy more effectively. One issue with TDM has been the slow turnaround of assay results, either necessitating an additional clinic visit for a sample or reacting to TDM results at a subsequent, rather than the current, dose. New point-of-care (POC) assays for mAbs are being developed that would potentially allow physicians to determine drug concentration quickly. However, work remains to understand how to determine what target exposure is needed for an individual patient, and whether the combination of POC assays and dashboards presents a safe approach with substantial outcome benefit over the current standard of care.