American Gastroenterological Association Institute Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Diseases

Abstract

Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease. To inform these clinical guidelines, this technical review was developed in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework for interventional and prognostic studies, and focused on the application of TDM for biologic therapy, specifically anti-tumor necrosis factor-α agents, and for thiopurines. Focused questions address the benefits and risks of a strategy of reactive TDM (in patients with active inflammatory bowel disease) to guide treatment changes compared with empiric treatment changes, and the benefits and risks of a strategy of routine proactive TDM (during routine clinical care in patients with quiescent disease) compared with no routine TDM. Additionally, the review addresses the benefits and risks of routine measurement of thiopurine methyltransferase enzyme activity or genotype before starting thiopurine therapy compared with empiric weight-based dosing and explores the performance of different trough drug concentrations for anti-tumor necrosis factor agents and thiopurines to inform clinical decision making when applying TDM in a reactive setting. Due to a paucity of data, this review does not address the role of TDM for more recently approved biologic agents, such as vedolizumab or ustekinumab.

Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease

“…In attempts to clarify cut‐off values, data from different reports were combined. In a pooled analysis involving both CD and UC, the proportion of patients not in clinical remission decreased from 17% at an adalimumab threshold of 5.0 µg/mL compared to 10% at a threshold of 7.5 µg/mL, suggesting that previously reported cut‐off values might be too low. A meta‐analysis of six studies involving 536 patients with CD was performed in 2014 .…”

Anti-TNF Therapy in Crohn’s Disease

“…Based on the currently available evidence (often scanty), the suggested target trough concentrations are >5 mg/mL for infliximab, >7.5 mg/mL for adalimumab, and >20 mg/mL for certolizumab pegol. These are proposed as guides to decide whether escalation of therapy may be beneficial (if trough is below this threshold) compared with switching therapy (to be considered if trough is above this threshold) to achieve clinical response in patients who are experiencing secondary loss of response on maintenance therapy [100]. For asymptomatic patients with ongoing endoscopic activity or with perianal disease [101] who undergo reactive TDM, target trough concentrations may be higher, such that escalating index therapy may be a preferable option before switching therapies in these settings.…”

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

“…There has been limited guidance on the use of TDM with vedolizumab. The recent American Gastroenterological Association guidelines and the Sydney IBD Consensus statements on TDM focused only on TNFα antagonists . The BRIDGe group recommended use of TDM in vedolizumab‐treated patients with primary nonresponse or secondary loss of response, primarily to determine the presence or absence of drug, but could not recommend optimal trough concentrations …”