OBJECTIVES : Algorithmic dose management based on serum concentrations and/or detection of anti-drug antibodies has the potential to be more effective than symptom-based dose escalation in inflammatory bowel disease (IBD) patients. The effectiveness of therapeutic drug monitoring (TDM) to improve clinical outcomes in IBD patients was assessed undertaking a critical literature review and meta-analysis.

METHODS : MEDLINE, EMBASE and Cochrane were searched up to 1 February 2019 for comparisons of proactive/reactive TDM with empiric care. Both pediatric and adult IBD populations were included, with no restrictions for TDM assay. One of the following outcomes had to be reported: clinical remission/response/relapse, endoscopic remission/response, surgery, hospitalization, drug discontinuation, immunomodulators/steroids concomitant therapy, and adverse events. Effect estimates were pooled separately for RCT/observational studies and congress abstracts using a random-effect model in case of heterogeneity>50%.

RESULTS : 12 papers were included, for a total of 2,243 patients (73% Crohn’s disease). TDM was associated with superior clinical response rate (OR=2.07, 95%CI 1.49-2.87), and inferior relapse/treatment failure (OR=0.28, 95%CI 0.11-0.76). There was also evidence of better clinical remission rate in TDM group although the significance threshold was not reached (OR=1.23, 95%CI 0.96-1.56). About 36% of patients treated to an adequate anti-TNFα trough concentration and no antibody detected failed the treatment; such patients could be better treated changing to a medication with a different mechanism of action (e.g. interleukin inhibitors) instead of changing within anti-TNFα class. Probably due to better disease management, discontinuation rate was lower in TDM group (OR=0.50, 95%CI 0.27-0.94); furthermore, favorable outcomes related to hospitalization (OR=0.47, 95%CI 0.23-0.98) and IBD related surgery (OR=0.46, 95%CI 0.31-0.70) rates were observed.

CONCLUSIONS : Evidence of this meta-analysis appears to support an association between TDM strategy and superior clinical outcomes (particularly response and relapse) and better disease management. Results suggest a potential safety benefit and cost savings due to hospitalization and surgery reductions.