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

Abstract

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 No TDM: 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 no TDM 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 No TDM: 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.

Therapeutic drug monitoring of anti‐tumour necrosis factor‐α agents in inflammatory bowel disease: Limits and improvements

“…The available evidence is limited and of low quality, so it is difficult to ensure that 1 strategy is better than the other. 2 Retrospective designs and low power of the studies are still problems. We reach the same conclusions as Sha et al 2 and Ricciuto et al 20 : since the AGA recommendations, no prospective studies have been published to help clarify this issue.…”

“…2 Retrospective designs and low power of the studies are still problems. We reach the same conclusions as Sha et al 2 and Ricciuto et al 20 : since the AGA recommendations, no prospective studies have been published to help clarify this issue. Regarding individualized dosing methods, although there are several published methods, the most widely used in IBD are those based on population PK.…”

“…The management of anti-tumour necrosis factor-α (TNFα) 1 drugs in inflammatory bowel disease (IBD) has made significant progress in the last decade. 2 The discovery of new mechanisms of action and the optimization of conventional treatments have led to an important change in clinical management.…”

Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

“…Systematic reviews and meta-analysis performed to resolve this deadlock have consistently shown no clear benefit of any TDM strategy over empiric optimization. The reviews have shown a consistent cost benefit with a reactive TDM strategy vs. empiric escalation ( 31 ) and drug durability benefit with the proactive strategy ( 32 , 33 ). This assumes greater importance in pediatrics as IBD specialists try to factor in insurance coverage and payor–payee concerns into pharmacotherapeutic decision-making ( 34 ).…”

Highs and Lows of Proactive Therapeutic Drug Monitoring in Crohn’s Patients

“…Nevertheless, given the relative novelty of TDM and gaps in the literature, there continues to be uncertainty regarding the logistics of how and when to apply TDM into clinical practice [3]. Unresolved questions include how should TDM be performed-proactive monitoring vs reactive monitoring, how often should proactive testing be performed, which patients benefit most from TDM, how to interpret and respond to the results, and which are the most appropriate concentrations to target.…”