scholarly journals Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Akshay Kapoor ◽  
Eileen Crowley
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Dose Individualization ◽  
Loss Of Response ◽  
Fixed Weight ◽  
Inflammatory Bowel

In the current era of treat-to-target strategies, therapeutic drug monitoring (TDM) has emerged as a potential tool in optimizing the efficacy of biologics for children diagnosed with inflammatory bowel disease (IBD). The incorporation of TDM into treatment algorithms, however, has proven to be complex. “Proactive” TDM is emerging as a therapeutic strategy due to a recently published pediatric RCT showing a clear benefit of “proactive” TDM in anti-TNF therapy. However, target therapeutic values for different biologics for different disease states [ulcerative colitis (UC) vs. Crohn's disease (CD)] and different periods of disease activity (induction vs. remission) require further definition. This is especially true in pediatrics where the therapeutic armamentarium is limited, and fixed weight-based dosing may predispose to increased clearance leading to decreased drug exposure and subsequent loss of response (pharmacokinetic and/or immunogenic). Model-based dosing for biologics offers an exciting insight into dose individualization thereby minimizing the chances of losing response. Similarly, point-of-care testing promises real-time assessment of drug levels and individualized decision-making. In the current clinical realm, TDM is being used to prolong drug durability and efficacy and prevent loss of response. Ongoing innovations may transform it into a personalized tool to achieve optimal therapeutic endpoints.

scholarly journals The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Robert A. Mitchell ◽  
Constantin Shuster ◽  
Neal Shahidi ◽  
Cherry Galorport ◽  
Mari L. DeMarco ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Statistical Significance ◽  
Therapeutic Drug ◽  
Loss Of Response ◽  
Remission Rates ◽  
Inflammatory Bowel ◽  
Group 3

Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P=0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

scholarly journals Immunogenicity of biologics used in the treatment of inflammatory bowel disease: A review

2021 ◽  
pp. 1-11
Author(s):  
Mariam Bqain ◽  
Alex Efimov ◽  
David Baker ◽  
Angray S. Kang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Clinical Symptoms ◽  
British Society ◽  
Therapeutic Drug ◽  
Loss Of Response ◽  
Alternative Drug ◽  
Inflammatory Bowel

PURPOSE OF THE REVIEW: Here we critically evaluate the literature on immunotherapy failure in inflammatory bowel disease patients. In particular anti-drug antibody production, and subsequently loss of response as the primary cause of immunotherapy failure in IBD patients. The benefits of shifting from the “standard” empirical dose escalation approach to therapeutic drug monitoring with anti-TNFα therapy is explored. RECENT FINDINGS: The American Gastroenterology Association and British Society of Gastroenterology both currently recommend the use of reactive therapeutic drug monitoring to guide treatment, following loss of response in inflammatory bowel disease patients with active disease. However, further research is required to prove the efficacy of a proactive therapeutic drug monitoring approach alone in remitted IBD patients. SUMMARY: A combination of personalised monitoring approach for anti-drug antibodies and therapeutic drug monitoring could provide beneficial treatment outcome for people with inflammatory bowel disease by predicting drug failure prior to clinical symptoms and allowing timely switching to an alternative drug.

scholarly journals Proactive versus Reactive Therapeutic Drug Monitoring: Why, When, and How?

2021 ◽  
pp. 1-9
Author(s):  
Manar Shmais ◽  
Miguel Regueiro ◽  
Jana G. Hashash
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Loss Of Response ◽  
Inflammatory Bowel ◽  
Necrosis Factor

<b><i>Background:</i></b> Up to a third of inflammatory bowel disease) patients show primary nonresponse to antitumor necrosis factor (anti-TNF) biological therapy, and of those who respond, up to 40% develop secondary loss of response (LOR). Therapeutic drug monitoring (TDM) plays a crucial role in assessing patients with LOR to guide therapy by giving more of the drug or switching to a different biological agent. Although reactive TDM is suggested or recommended by the majority of gastroenterology associations, proactive TDM seems to be more controversial. <b><i>Summary:</i></b> In this article, we discuss the updated guidelines on TDM and will also discuss the available data supporting proactive and reactive TDM in patients with Crohn’s disease and those with ulcerative colitis using the different available biological agents. <b><i>Key Messages:</i></b> Therapeutic drug monitoring (TDM) is a valuable tool to aid in inflammatory bowel disease (IBD) therapy optimization. Reactive TDM is widely accepted in IBD patients with suspected loss of response, especially in those receiving antitumor necrosis factor (anti-TNF) agents. Proactive TDM is emerging as a reasonable approach to patients initiated on anti-TNF therapy, specifically infliximab and, to some extent, adalimumab, particularly for patients with severe ulcerative colitis and fistulizing Crohn’s disease. Similarly, TDM may play a role in patients considering de-escalation from combination therapy. To date, proactive TDM is not widely applied to ustekinumab and vedolizumab and more data are required before this becomes part of clinical practice.

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