Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring

Abstract

Inflammatory bowel disease (IBD) is a chronic condition that significantly affects the quality of life of its patients. Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution, there remains a proportion of patients that do not respond or lose response to treatment. Therapeutic drug monitoring (TDM) involves measuring levels of serum drug concentrations and anti-drug antibodies. TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases. This was then introduced in IBD to rationalize primary non-response or secondary loss of response, given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure. The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations, in everyday practice. A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management, through an electronic search using PubMed and ScienceDirect. TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment. Despite a trend towards an association between clinical outcomes and drug concentrations, proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes. In the clinical setting, TDM has proven to be useful in managing IBD patients, and its use in the reactive setting, as an additional tool to help manage patients with treatment failure, is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.

Non-medical switch from the originator to biosimilar and between biosimilars of adalimumab in inflammatory bowel disease – a prospective, multicentre study

“…Further limitation to our study that ADA serum drug trough level and antidrug antibody measurements (TDM-therapeutic drug monitoring) were not performed. Nonetheless, the impact of TDM measurements on the clinical decision making and the correlation with clinical outcomes in ADA treated patients is less important compared to patients treated with infliximab [26] .…”

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place

“…The article presented by Albader et al [ 1 ] titled “Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring” addresses a controversial topic in clinical practice: The role of therapeutic drug management in patients with inflammatory bowel disease (IBD).…”

“…TDM was regarded with great hope. But, as recognized by Albader et al [ 1 ], implementation of TDM in clinical practice was challenged by few factors including uncertainty of the optimal cut-off values, assay variable sensitivity in detecting drug levels and antibodies and, most importantly, individual pharmacokinetics influenced by severity of the disease and body weight[ 4 - 6 ].…”

“…This controversy arises in part due to the differences in study design including different outcomes: Clinical, endoscopic, histologic response and/or cost efficiency but also due to timing of TDM implementation proactive vs reactive to sLOR. The author concluded that it is “difficult to prove that proactive TDM is associated with better therapeutic outcomes” but it should be considered an addition to the other tools already routinely used in practice including biomarkers (calprotectine), imaging, capsule endoscopy[ 1 ].…”

Therapeutic drug monitoring in inflammatory bowel disease treatments

“…We read with interest the review by Albader et al [ 1 ] on the application of therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD). The authors provided a comprehensive overview of the relationship between proactive or reactive TDM and clinical outcomes.…”