A 3‐year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease

Abstract

Aims: Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep-TDM) programme for dose adjustment. Methods: A 3-year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep-TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD-related surgery and IBD-related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis. Results: In the mep-TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27-0.92; P = .037), IBD-related surgery (HR: 0.14; 95% CI:0.03-0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17-0.87; P = .022). SIRs were lower in the mep-TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999).Conclusion: This study found that compared to empirical dosing, mep-TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD-related hospitalization and surgery and incidence of SIRs, and increasing long-term durability of treatment effects. K E Y W O R D Sinflammatory bowel diseases, infliximab, personalized medicine, therapeutic drug monitoring

Fecal Lactoferrin Predicts Primary Nonresponse to Biologic Agents in Inflammatory Bowel Disease

“…2]. More recently, proactive TDM has been proposed as a tool to optimize initial drug treatment in these patients [4][5][6]. With proactive TDM, target TL are stipulated before induction and -when measured and found subtherapeutic (in the absence of ADA) during and after induction -the drug dose is progressively increased.…”

“…With proactive TDM, target TL are stipulated before induction and -when measured and found subtherapeutic (in the absence of ADA) during and after induction -the drug dose is progressively increased. A number of studies have indeed shown that this interesting strategy could reduce PNR incidence and improve long-term outcomes [4][5][6]. However, solid evidence for routine clinical use is still lacking [12,13].…”

“…Primary response to biologic induction in inflammatory bowel disease (IBD) -both ulcerative colitis (UC) and Crohn's disease (CD) -has been traditionally evaluated by the attenuation of clinical symptoms after 12 weeks [1,2]. More recently, the measurement of drug trough levels (TL) and of antidrug antibodies (ADA), a strategy known as therapeutic drug monitoring (TDM), has been used to evaluate possible loss of response (LOR) [3] and proposed by some to proactively reduce primary nonresponse (PNR) and LOR incidence [4][5][6]. Although proactive TDM-based management might improve outcomes in IBD [4][5][6], this strategy is expensive and has practical shortcomings [7][8][9][10][11] and it is unclear whether it Fecal Lactoferrin and Primary Nonresponse 627 Dig Dis 2021;39:626-633 DOI: 10.1159/000515432 is truly superior to reactive TDM or to the clinically based management [12,13].…”

“…More recently, the measurement of drug trough levels (TL) and of antidrug antibodies (ADA), a strategy known as therapeutic drug monitoring (TDM), has been used to evaluate possible loss of response (LOR) [3] and proposed by some to proactively reduce primary nonresponse (PNR) and LOR incidence [4][5][6]. Although proactive TDM-based management might improve outcomes in IBD [4][5][6], this strategy is expensive and has practical shortcomings [7][8][9][10][11] and it is unclear whether it Fecal Lactoferrin and Primary Nonresponse 627 Dig Dis 2021;39:626-633 DOI: 10.1159/000515432 is truly superior to reactive TDM or to the clinically based management [12,13]. Ideally, it is the individual patient disease burden that should be targeted by therapy [14][15][16].…”

Mechanistic Modelling Identifies and Addresses the Risks of Empiric Concentration-Guided Sorafenib Dosing

“…Therapeutic drug monitoring (TDM) is an established method to facilitate concentration-guided dose adaption but requires significant clinical and analytical resources to quantify the drug of interest and establish a robust evidence base. To date, few cancer medicines have met the level of evidence required to implement TDM in a clinical setting [ 21 , 22 , 23 ].…”