Is Therapeutic Drug Monitoring For Anti-Tumour Necrosis Factor Agents In Adults With Inflammatory Bowel Disease Ready For Standard Of Care? A Systematic Review And Meta-Analysis

Introduction: Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions.Methods: We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts' definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology.Results: We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs NoTDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88-1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the noTDM group [RR: 0.60; 95% CI 0.35-1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15-0.32]. PICO 4 TDM [proactive/reactive] vs NoTDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77-1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE.Conclusions: This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.