Introduction: Tumor necrosis factor (TNF) antagonists have revolutionized the treatment of inflammation-causing diseases. Although impactful, they present several challenges. The biggest obstacle is an inadequate therapeutic response. When patients lose response following the initial treatment phase, clinicians obtain serum drug concentrations and anti-drug antibody levels. Rather than taking a reactive approach, some physicians are beginning to utilize therapeutic drug monitoring (TDM) proactively. Although proactive usage of TDM is becoming more prevalent, it is inconsistently utilized. The purpose of this study is to establish when TDM of anti-TNF mAbs is occurring and to determine how these findings guide clinical decision making.
Methods: This systematic scoping review assessed literature from Medline 1946-2020, Embase 1974 -2020, Cochrane Library 1898 – 2020, CENTRAL ClinicalTrials.gov, EU Clinical Trials Register, ISRCTN registry, and WHO International Clinical Trials Registry Platform using a series of search terms. Eligible articles were reviewed and content summarized using two primary reviewers. Articles that discussed anti-TNF medications or anti-TNF therapy, clinical usage of anti-TNF medications, anti-TNF therapeutic drug monitoring, discussion of proactive and/or reactive TDM, discussion of drug monitoring using drug trough levels, and study participants of any sex and age were included in this study.
Results: The search yielded 3,478 articles. The titles and abstracts of 1,322 articles were screened and excluded 975 articles; 347 studies went through a full-text review. Two hundred thirty-eight of these articles failed to meet inclusion criteria, leaving 109 papers to be included for analysis. While all of the papers discussed the usage of TDM, 59 papers discussed using proactive TDM during the induction phase, and 47 of the studies assessed reactive TDM during the maintenance phase. 93 studies demonstrated improved clinical outcomes if clinicians engaged in proactive or reactive TDM during the patient’s treatment.
Conclusions: Considering that TDM during any phase is highly correlated to therapeutic improvement, the earlier intervention enabled by TDM during the induction phase could provide a timelier transition to improved therapy.
Responses
Asheley – very nice scoping review. This work gives me a clear picture on how TDM was used to support decision making of the use of anti-TNB mAbs.
The related question is that whether the use of TDM actually leads to improvement of patient outcomes. what kind of study design was used? RCT? Any SR/MA that have looked to sort out the “effect” of TDM. I believe that RCT design is needed or it could be observational study which controls selection bias and confounding very well. Did you come up with any good RCTs or SR/MA that answer this question directly?
Thank you, Dr. Chaiyakunapruk. Great question! The Trough Concentration Adapted Infliximab Treatment (TAXIT) trial assessed proactive usage of TDM in adults treated with infliximab for IBD. In the proactive TDM arm of the study, clinicians were able to optimize therapy based on low trough levels. They were ultimately able to achieve clinical and biochemical remission of IBD compared to those with no TDM. Although proactive treatment improved outcomes, there was no difference after one year of therapy. This finding suggested that while proactive TDM may initially lead to better outcomes during a short-term period, it may not benefit those requiring treatment for more than one year.
Ideally, an RCT would be most beneficial to determine the effect of TDM in Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis, as TDM may be more beneficial in one disease state versus another.
Excellent response. Scholarly and clear!
Thank you for your research.
Ashley, this work has come together so nicely. What a great discovery to see that proactive TDM can make such a difference in patient outcome! I’m assuming you’ll be publishing this?
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