Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases

Abstract

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 [ strongly disagree and 10 [ strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ‡7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. RESULTS: The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. CONCLUSION: Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

“…Therapeutic drug monitoring (TDM) has been recognised as an important strategy to inform clinical decision‐making in patients with inflammatory bowel diseases (IBD) . The rationale for TDM is that a systematic and algorithmic assessment of drug concentration and anti‐drug antibodies may help objectively evaluate potential reasons for failure of therapy and define next steps in management, and proactively provide opportunities for optimising therapy.…”

“…The recent American Gastroenterological Association guidelines and the Sydney IBD Consensus statements on TDM focused only on TNFα antagonists . The BRIDGe group recommended use of TDM in vedolizumab‐treated patients with primary nonresponse or secondary loss of response, primarily to determine the presence or absence of drug, but could not recommend optimal trough concentrations …”

“…Therapeutic drug monitoring (TDM) has been recognised as an important strategy to inform clinical decision-making in patients with inflammatory bowel diseases (IBD). [1][2][3] The rationale for TDM is that a systematic and algorithmic assessment of drug concentration and anti-drug antibodies may help objectively evaluate potential reasons for failure of therapy and define next steps in management, and proactively provide opportunities for optimising therapy. This is based on clinical observations including: (a) inter-individual variability in drug clearance through both immune-mediated (formation of neutralising anti-drug antibodies) and non-immune-mediated mechanisms (associated with high inflammatory burden) which contribute to differences in drug concentration, (b) presence of an exposure-response relationship, wherein serum drug concentration is associated with magnitude of the clinical response, and (c) concept of mechanistic failure, wherein despite adequate drug exposure at site of receptor, some patients may not respond to a particular class of biologics due to differences in underlying disease pathophysiology.…”

“…2,13,14 The BRIDGe group recommended use of TDM in vedolizumab-treated patients with primary nonresponse or secondary loss of response, primarily to determine the presence or absence of drug, but could not recommend optimal trough concentrations. 3 Hence, we conducted a systematic review and meta-analysis to evaluate the association between vedolizumab trough concentrations and clinical outcomes in patients with IBD, and evaluated serum drug trough concentrations associated with superior efficacy.…”

Therapeutic Drug Monitoring of Biologic Agents in the Era of Precision Medicine

“…TDM in biologic therapy refers to the evaluation of trough drug concentration and anti-drug antibody to help optimize the dosage regimen or select the right agents. Previous studies have shown positive correlations between drug concentrations and good clinical or laboratory outcomes, whereas low or undetectable drug concentrations can lead to immunogenicity and treatment failure [4,5]. Loss of response is currently the major problem encountered in anti-tumor necrosis factor therapy.…”