Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: Translating TNF-α experience to oncology

2015 ◽  
Vol 99 (4) ◽  
pp. 419-431 ◽  
Author(s):  
TH Oude Munnink ◽  
MJ Henstra ◽  
LI Segerink ◽  
KLL Movig ◽  
P Brummelhuis-Visser
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Malignant Disease ◽  
Therapeutic Drug ◽  
Tnf Α

Is There a Role for Therapeutic Drug Monitoring of Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 70-77 ◽  
Author(s):  
Filip Baert
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Treatment Guidelines ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Short Term ◽  
Clear Dose Response ◽  
Inflammatory Bowel

In recent years it has become clear that therapeutic drug monitoring can be an important tool to optimize outcome and costs of anti TNF treatment including the subcutaneous and fully human monoclonal antibodies. There is a clear dose response curve between early serum concentrations of all monoclonal antibodies and response both short term and long term. The wide variations in early serum concentrations are insufficiently explained by classic pharmacokinetic factors. Low early concentrations can lead to anti-drug antibody formation and ensuing loss of response. Therapeutic drug monitoring allows to rationalize the current practice of dose optimization and the use of concomitant immunomodulator treatment. However more prospective studies are needed before strong recommendations can enter treatment guidelines.

scholarly journals The First WHO International Standard for Adalimumab: Dual Role in Bioactivity and Therapeutic Drug Monitoring

2021 ◽  
Vol 12 ◽  
Author(s):  
Meenu Wadhwa ◽  
Chris Bird ◽  
Eleanor Atkinson ◽  
Isabelle Cludts ◽  
Peter Rigsby
Keyword(s):  
Life Cycle ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Life Cycle Management ◽  
World Health ◽  
Therapeutic Drug ◽  
Expert Committee ◽  
Safety And Efficacy ◽  
International Standard ◽  
Tnf Α

The expanded availability of adalimumab products continues to widen patient access and reduce costs with substantial benefit to healthcare systems. However, the long-term success of these medicines is highly dependent on maintaining consistency in quality, safety and efficacy while minimizing any risk of divergence during life-cycle management. In recognition of this need and demand from global manufacturers, the World Health Organization (WHO) Expert Committee on Biological standardization established the WHO 1st International standard (IS) for Adalimumab (coded 17/236) in October 2019 with a defined unitage ascribed to each of the individual bioactivities evaluated in the study namely, TNF-α binding, TNF-α neutralization, complement dependent cytotoxicity and antibody-dependent cellular cytotoxicity. For development of the IS, two candidate standards were manufactured as per WHO recommendations. Analysis of extensive datasets generated by testing of a common set of samples including the candidate standards by multiple stakeholders including regulatory agencies using their own qualified assays in a large international collaborative study showed comparable biological activity for the tested candidates for the different activities. Use of a common standard significantly decreased the variability of bioassays and improved agreement in potency estimates. Data from this study clearly supports the utility of the IS as an important tool for assuring analytical assay performance, for bioassay calibration and validation, for identifying and controlling changes in bioactivity during life-cycle management and for global harmonization of adalimumab products. In addition, in a separate multi-center study which included involvement of hospital and clinical diagnostic laboratories, the suitability of the adalimumab IS for therapeutic drug monitoring assays was examined by analysis of data from testing of a common blind coded panel of adalimumab spiked serum samples representative of the clinical scenario along with the IS and in-house standards in diverse immunoassays/platforms. Both commercially available and in-house assays that are routinely used for assessing adalimumab trough levels were included. Excellent agreement in estimates for adalimumab content in the spiked samples was observed regardless of the standard or the method with inter-laboratory variability also similar regardless of the standard employed. This data, for the first time, provides support for the extended applicability of the IS in assays in use for therapeutic drug monitoring based on the mass content of the IS. The adalimumab IS, in fulfilling clinical demand, can help toward standardizing and harmonizing clinical monitoring assays for informed clinical decisions and/or personalized treatment strategies for better patient outcomes. Collectively, a significant role for the adalimumab IS in assuring the quality, safety and efficacy of adalimumab products globally is envisaged.

scholarly journals Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonello Di Paolo ◽  
Giacomo Luci
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Personalized Medicine ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Individual Characteristics ◽  
Therapeutic Drug ◽  
Therapeutic Effects ◽  
Primary Resistance ◽  
Inflammatory Bowel

The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.

Therapeutic drug monitoring of anti-TNF-α agents in inflammatory bowel diseases

2015 ◽  
Vol 15 (8) ◽  
pp. 1107-1117 ◽  
Author(s):  
Carla Felice ◽  
Manuela Marzo ◽  
Daniela Pugliese ◽  
Alfredo Papa ◽  
Gian Lodovico Rapaccini ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Inflammatory Bowel Diseases ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel
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