CT-P13 is the first subcutaneous infliximab molecule approved for the management of inflammatory bowel disease (IBD). Compared to intravenous therapy, SC infliximab offers a range of practical, micro- and macroeconomic advantages. Data from the rheumatological literature suggest that subcutaneous CT-P13 may lead to superior disease outcomes in comparison to intravenous infliximab. Existing studies in IBD have focussed on pharmacokinetic comparisons and are inadequately powered to evaluate efficacy and safety differences between the two modes of administration. However, emerging clinical trial and real-world data support comparable clinical, biochemical, endoscopic and safety outcomes between subcutaneous and intravenous infliximab in both luminal Crohn’s disease and ulcerative colitis. Across the available data, subcutaneous CT-P13 provides relative pharmacokinetic stability and higher trough drug levels when compared to intravenous administration. The clinical impact of this observation on immunogenicity and treatment persistence is yet to be determined. Trough levels between the two methods of administration should not be compared in isolation as any subcutaneous advantage must be considered in the context of comparable total drug exposure and the theoretical disadvantage of lower peak concentrations compared to intravenous therapy. Furthermore, target drug levels for subcutaneous CT-P13 associated with remission are not known. In this review, we present the available literature surrounding the pharmacokinetics of subcutaneous CT-P13 in the context of therapeutic drug monitoring and highlight the potential significance of these observations on the clinical management of patients with IBD.

The pathogenesis of inflammatory bowel disease (IBD) is complex and multifactorial. Undertreated disease has substantial individual and societal consequences. Current patient classification and subsequent positioning of IBD therapy are based on crude, readily accessible clinical data. These broad parameters are unlikely to reflect underlying molecular profiles and may account for the observed heterogeneity in treatment response. Precision medicine offers identification and integration of molecular profiles into clinical decision-making. Despite several promising scientific and technological advances, the pathogenesis and targetable molecular drivers of IBD remain incompletely understood. Precision medicine therefore remains aspirational. This comprehensive narrative review describes our current understanding of IBD pathophysiology, highlights preliminary genetic, immunological and microbial predictors of treatment response and outlines the role of ‘big data’ and machine learning in the path towards precision medicine.

Concomitant immunomodulation is utilised in combination with anti-TNF therapy for IBD primarily to increase drug levels and prevent anti-drug antibody formation. Whilst thiopurines have traditionally been the immunomodulator of choice in IBD populations, there are concerns regarding the long-term safety of the prolonged use of these agents: particularly an association with lymphoproliferative disorders. Given this, we have explored the existing literature on the use of low-dose oral methotrexate as an alternative immunomodulator for this indication. Although there is a lack of data directly comparing the efficacies of methotrexate and thiopurines as concomitant immunomodulators, the available literature supports the use of methotrexate in improving the pharmacokinetics of anti-TNF agents. Furthermore, low-dose oral methotrexate regimens appear to have comparable efficacies to higher-dose parenteral administration and are better tolerated. We suggest that clinicians should consider the use of low-dose oral methotrexate as an alternative to thiopurines when the primary purpose of concomitant immunomodulation is to improve anti-TNF pharmacokinetics.

Therapeutic Drug Monitoring (TDM) has an important role in the management of inflammatory bowel disease (IBD) patients on infliximab (IFX) or adalimumab and is recommended in IBD patients presenting a loss of response under anti TNF agent. But, TDM was not recommended for others biotherapies. Analyzing all publications about TDM and biologics in IBD patients, we reported the major results for each biotherapy. Emerging data suggest that TDM will probably be similarly useful forIFX SC. In contrast, there is no demonstrated clinical benefit to the use of TDM with golimumab. For vedolizumab results for the use of both reactive and proactive TDM are discordant. For ustekinumab, data supports the existence of an exposure response relationship, albeit of a lesser magnitude than with anti-TNF agents. Finally, recent data from small case series suggests that TDM could be valuable in optimizing anti-IL23 agents, particularly risankizumab, but this requires further clarification. Consistent with the new concept of 'proactive' strategy, recent data support the utility of dashboard-driven model informed precision dosing (MIDP) of anti-TNF agents, in particular infliximab. Dashboards are software systems using Bayesian population pharmacokinetic modelling to individualize recommendations for target drug levels.