Clinical Outcomes With Therapeutic Drug Monitoring in Inflammatory Bowel Disease: A Systematic Review With Meta-Analysis

Abstract

The existing limited evidence does not support an association between any TDM strategy and superior clinical remission rates but does support a cost savings benefit [particularly for reactive TDM] and suggests a potential benefit for anti-TNF durability [particularly proactive TDM]. Additional, longer-term studies are needed, particularly to further investigate proactive TDM, and to generate data on other anti-TNF agents, the induction period and paediatric populations.

The effects of proactive therapeutic drug monitoring vs reactive therapeutic drug monitoring in a virtual biologic clinic, a retrospective cohort study

“…Many IBD experts believe that proactive‐TDM leads to timely escalation of therapy, higher clinical remission rates, reduced immunogenicity (the development of clinically significant antibodies to IFX), cost reduction and a reduction in the loss of response to IFX . A recently published systematic review on the clinical outcomes of therapeutic drug monitoring in IBD included nine studies and found that there was not sufficient evidence to support one method of therapeutic drug monitoring (Reactive vs Proactive) over the other, in particular relating to clinical remission rates but did recognise that there was a potential for cost reduction with reactive therapeutic drug monitoring (reactive‐TDM) . As a consequence, the present guidelines advise that there is a lack of sufficient evidence to introduce the routine use of proactive‐TDM in the treatment of IBD patients.…”

“…The AGA advised that based on the research available at the time of the guideline, there was insufficient evidence to support the routine use of proactive‐TDM; however, the guideline failed to mention a number of important factors when reviewing the effectiveness of proactive‐TDM. A major omission in the guideline published by the AGA was the exclusion of the development of anti‐drug antibodies to IFX as an endpoint and a second major endpoint that was missing from the guideline was the discontinuation of IFX therapy . The European Crohn's and Colitis Organisation's guidelines on the management of ulcerative colitis (UC) acknowledge that therapeutic drug monitoring is being increasingly adopted to try to optimise outcomes, particularly during maintenance treatment but does not conclude with a specific recommendation for therapeutic drug monitoring …”

“…Limitations of the study include randomisation of patients already in the maintenance phase of IFX therapy who already had a clinical response to IFX. Furthermore, only 5% of patients were receiving combination therapy with Azathioprine (IFX‐immunomodulator combination therapy) which is not reflective of real‐world practice . Studies such as the SONIC trial have shown the benefits of IFX‐immunomodulator combination therapy for achieving higher rates of corticosteroid‐free remission …”

“…Issues with previous observational studies investigating proactive‐TDM include short duration of follow‐up, studies that are underpowered and that have failed to demonstrate superiority in clinical remission rates …”

Is the Combination of Pharmacokinetic and Pharmacodynamic Monitoring of Infliximab-Treated Patients the Way Forward?

“…3 Higher serum biological drug concentrations, lower fecal calprotectin levels, and a tight disease control approach are associated with favorable therapeutic outcomes in CD. 4,5 However, the best strategy for CD monitoring and its implications on treatment decisions has yet to be defined. The CALM Q5 trial conducted by Colombel et al 5 showed…”