Editorial: Is There a Role for Therapeutic Drug Monitoring of Subcutaneous Infliximab in Patients With Inflammatory Bowel Disease?

Abstract

Numerous exposure–outcome relationship studies demonstrate a positive correlation between therapeutic biologic drug concentrations and favourable outcomes in immune-medicated inflammatory disorders including inflammatory bowel disease (IBD) [1, 2]. In the same vein, low drug concentrations are associated with loss of response and immunogenicity [1, 3]. Furthermore, post hoc analyses of randomised controlled trials demonstrate that drug concentrations in the lowest quartile have similar outcomes to patients receiving placebo (Figure 1). Numerous guidelines and consensus statements recommend the use of proactive and reactive therapeutic drug monitoring (TDM) with intravenous infliximab (iv-IFX) and adalimumab [4]. However, there is limited data on the role of TDM for sc-IFX [5].

A well-designed study by Hong et al. greatly adds to the literature on TDM for sc-IFX in Crohn's disease (CD) [6]. They identified 124 patients with CD who received sc-IFX maintenance therapy for ≥ 6 months and showed that trough drug concentrations were higher in patients with mucosal healing (SES = 0) than in those without mucosal healing (24.1 vs. 16.9 μg/mL, p = 0.001). Similarly, patients with transmural healing (simplified magnetic resonance index of activity score of 0) had higher sc-IFX concentrations than those without transmural healing (26 vs. 20.5 μg/mL, p = 0.007). Receiver operating characteristic (ROC) analysis identified a sc-IFX threshold of 17.5 μg/mL for mucosal healing and 30.3 μg/mL for transmural healing. Furthermore, multivariate logistic regression showed that sc-IFX concentration was significantly associated with both mucosal (p = 0.002) and transmural healing (p = 0.005).

These findings are similar to previous studies showing that higher sc-IFX concentrations are associated with positive outcomes [7, 8]. In a retrospective study including 71 patients with IBD, sc-IFX concentrations were higher in patients with sustained clinical remission, composite clinical and biomarker remission, biochemical remission and deep remission (clinical, biological and biochemical remission) compared to patients who did not achieve these outcomes [7]. This study also identified a sc-IFX concentration of 20 μg/mL to be associated with deep remission [7]. A multicenter observational study of 220 patients with IBD in clinical remission who switched from iv-IFX to sc-IFX demonstrated that sc-IFX concentrations were significantly higher in patients who were in combined clinical and biochemical remission at week 12 [8]. Based on ROC analysis the optimal sc-IFX concentration cut-off for clinical and biochemical remission was 12.2 at week 12 and 13.2 μg/mL at week 52 [8]. These sc-IFX concentration cut-offs seem much higher than the previously identified ones for iv-IFX [1, 2]. This is similar to the pivotal CT-P13 RCTs where the mean (SD) week 22 trough sc-IFX concentration was 21.5 (9.9) μg/mL compared with 2.9 (2.6) μg/mL in the intravenous arm [9].

In conclusion, the current study provides further evidence that higher sc-IFX concentrations are associated with favourable outcomes in patients with IBD. This suggests that TDM may be as important for sc-IFX as it is for iv-IFX. Nevertheless, the therapeutic threshold for sc-IFX appear to be much higher (possibly 15–20 μg/mL or even higher) than what we are used to for iv-IFX (typically 5–10 μg/mL). Future research is needed to confirm these results and the role of TDM with sc-IFX.

Konstantinos Papamichael: conceptualization, writing – original draft, writing – review and editing, visualization. Adam S. Cheifetz: conceptualization, writing – original draft, writing – review and editing.

Konstantinos Papamichael: lecture fees from Mitsubishi Tanabe Pharma and Physicians Education Resource LLC; consultancy fee from Prometheus Laboratories Inc.; and scientific advisory board fees from ProciseDx Inc., Scipher Medicine Corporation and Celltrion Inc. Adam S. Cheifetz: Consulting: Abbvie, Adiso, Artizan (SAB), Bristol Myers Squibb, Clario, Food is Good, Fresenius Kabi, Fzata, Janssen, Pfizer, Prometheus (SAB), ProciseDx, Spherix, Samsung, Protagonist and Takeda; and speaking (non-branded): Abbvie, BMS, Janssen.

This article is linked to Hong et al paper. To view this article, visit https://doi.org/10.1111/apt.18354.