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

Abstract

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.

Effectiveness and safety of biologics in pediatric inflammatory bowel disease: Real-life data from the Sicilian Network

“…Clinical trial results from as early as 2014, demonstrate the cost-effectiveness of TDM for anti-TNF-α agents and recent reports in pediatrics provide evidence that close TDM can help not only detect, but also reverse immunogenicity, with appropriate TDM-based dose adjustments [37].…”

Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model

“…While reactive TDM was consistently shown to affect response to treatment and aid decision‐making (32), whether proactive TDM offers an additional benefit over the reactive approach is a matter of an ongoing controversy. Nevertheless, recent studies have demonstrated a potential benefit of proactive TDM in terms of drug retention and a positive effect on exacerbations, treatment failure, and hospitalization rates in adults (33) and children (34). Our findings should be taken into account when planning treatment adjustment either reactively or proactively.…”

Selective Forms of Therapy in the Treatment of Inflammatory Bowel Diseases

“…In the pediatric population, the drug has not been approved yet, and the necessary clinical trials are underway. However, therapy is possible for patients who have exhausted the existing conventional methods of treatment, each time after obtaining the opinion of the ethics committee [15]. Among the indications other than IBD, the drug is used in plaque psoriasis in adults and children and adolescents [14].…”