BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 [ strongly disagree and 10 [ strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ‡7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. RESULTS: The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. CONCLUSION: Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn's Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.

BACKGROUND & AIMS Monitoring serum concentrations of tumor necrosis factor antagonists in patients receiving these drugs as treatment for inflammatory bowel disease (IBD), also called therapeutic drug monitoring, is performed either after patient loss of response (reactive drug monitoring) or in patients in clinical remission whose drug has been titrated to a target concentration (proactive drug monitoring). We compared long-term outcomes of patients with IBD undergoing proactive vs reactive monitoring of serum concentrations of infliximab. METHODS We performed a multicenter, retrospective study of 264 consecutive patients with IBD (167 with Crohn’s disease) receiving infliximab maintenance therapy. The subjects received proactive (n = 130) or reactive (n = 134) drug monitoring, based on measurements of first infliximab concentration and antibodies to infliximab, from September 2006 to January 2015; they were followed through December 2015 (median time of 2.4 years). We analyzed time to treatment failure, first IBD-related surgery or hospitalization, serious infusion reaction, and detection of antibodies to infliximab. Treatment failure was defined as drug discontinuation for loss of response or serious adverse event, or need for surgery. RESULTS Multiple Cox regression analysis independently associated proactive drug monitoring, compared with reactive monitoring, with reduced risk for treatment failure (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.09–0.27; P < .001), IBD-related surgery (HR, 0.30; 95% CI, 0.11–0.80; P = .017), IBD-related hospitalization (HR, 0.16; 95% CI, 0.07–0.33; P < .001), antibodies to infliximab (HR, 0.25; 95% CI, 0.07–0.84; P = .025), and serious infusion reaction (HR, 0.17; 95% CI, 0.04–0.78; P = .023). CONCLUSIONS In a retrospective analysis of patients with IBD receiving proactive vs reactive monitoring of serum concentration of infliximab, proactive monitoring was associated with better clinical outcomes, including greater drug durability, less need for IBD-related surgery or hospitalization, and lower risk of antibodies to infliximab or serious infusion reactions.

: Primary nonresponse and primary nonremission are important limitations of tumor necrosis factor (TNF) antagonists, occurring in 10% to 40% and 50% to 80% of patients with inflammatory bowel disease, respectively. The magnitude of primary nonresponse differs between phase III clinical trials and cohort studies, indicating differences, e.g., in definition, patient population or blinding. The causes of nonresponse can be attributed to the drug (pharmacokinetics, immunogenicity), the patient (genetics, disease activity), the disease (type, location, severity), and/or the treatment strategy (dosing regimen, combination therapy). Primary nonresponse has been attributed to "non-TNF-driven disease" which is an overly simplified and potentially misleading approach to the problem. Many patients with primary nonresponse could successfully be treated with dose optimization during the induction phase or switching to another TNF antagonist. Therefore, primary nonresponse is frequently not a non-TNF-driven disease. Recent studies from rheumatoid arthritis and preliminary data from inflammatory bowel disease evaluating therapeutic drug monitoring have suggested that early measurement of drug and anti-drug antibody concentrations could help to define primary nonresponse and rationalize patient management of this problem. Moreover, a modeling approach including pharmacological parameters and patient-related covariants could potentially be predictive for response to the treatment. We describe an overview of this evolution in thinking, underpinned by previous findings, and assess the potential role of early measurement of drug and antidrug antibody concentrations in the definition and management of primary nonresponse.