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Review
. 2018 Sep 5;20(6):99.
doi: 10.1208/s12248-018-0257-y.

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

Anne S Strik  1 , Yow-Ming C Wang  2 , Laura E Ruff  3 , William Yashar  3 , Bradley T Messmer  3 , Diane R Mould  4
Affiliations
Review

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

Anne S Strik et al. AAPS J. .

Abstract

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.

Keywords: dashboard; inflammatory bowel disease; monoclonal antibodies; point of care; therapeutic drug monitoring.

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Conflict of interest statement

Conflict of Interest AS Strik has received lecture fees from Merck Sharp & Dohme, Takeda, AbbVie, Mundipharma, Pfizer, Janssen-Cilag, and Tillots. DR Mould is the founder and president of Projections Research Inc., a consulting company that conducts population PK and PKPD evaluations for the pharmaceutical industry. Laura Ruff, William Yashar, and Bradley Messmer are all employed by Abreos Biosciences Inc., a company that produces point-of-care assays. While Y-MC Wang is an employee of the Food and Drug Administration (FDA), the scientific perspectives expressed herein do not represent the policy of the FDA.

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References

    1. Park JH, Peyrin-Biroulet L, Eisenhut M, Shin JI. IBD immunopathogenesis: a comprehensive review of inflammatory molecules. Autoimmun Rev. 2017;16(4):416–26. - PubMed
    1. de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016;13(1):13–27. - PubMed
    1. Gomollon F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al.3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohn’s Colitis. 2017;11(1):3–25. - PubMed
    1. Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, et al.Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohn’s Colitis. 2017;11(7):769–84. - PubMed
    1. Passot C, Azzopardi N, Renault S, Baroukh N, Arnoult C, Ohresser M, et al.Influence of FCGRT gene polymorphisms on pharmacokinetics of therapeutic antibodies. MAbs. 2013;5(4):614–9. - PMC - PubMed

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