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.

大量暴露-结果关系研究表明，治疗性生物药物浓度与免疫药物炎症性疾病（包括炎症性肠病 （IBD））的良好结果呈正相关 [1， 2]。同样，低药物浓度与反应和免疫原性丧失有关 [1， 3]。此外，随机对照试验的事后分析表明，最低四分位数的药物浓度与接受安慰剂的患者具有相似的结果（图 1）。许多指南和共识声明推荐在静脉使用英夫利昔单抗（iv-IFX）和阿达木单抗时采用主动和反应性治疗药物监测（therapeutic drug monitoring， TDM）[4]。然而，关于 TDM 对 sc-IFX 的作用的数据有限 [5]。

Hong 等人精心设计的一项研究极大地丰富了克罗恩病 （CD） 中 sc-IFX 的 TDM 文献 [6]。他们确定了 124 名接受 sc-IFX 维持治疗 ≥ 6 个月的 CD 患者，并表明粘膜愈合患者 （SES = 0） 的谷药物浓度高于粘膜未愈合的患者 （24.1 vs. 16.9 μg/mL，p = 0.001）。同样，透壁愈合的患者 （简化磁共振活性指数评分为 0） 的 sc-IFX 浓度高于未透壁愈合的患者 （26 vs. 20.5 μg/mL，p = 0.007）。受试者工作特征 （ROC） 分析确定粘膜愈合的 sc-IFX 阈值为 17.5 μg/mL，透壁愈合的 sc-IFX 阈值为 30.3 μg/mL。此外，多变量 logistic 回归显示，sc-IFX 浓度与粘膜 （p = 0.002） 和透壁愈合 （p = 0.005） 显著相关。

这些发现与以前的研究相似，表明较高的 sc-IFX 浓度与积极结果相关 [7， 8]。在一项纳入 71 例 IBD 患者的回顾性研究中，与未达到这些结局的患者相比，持续临床缓解、复合临床和生物标志物缓解、生化缓解和深度缓解（临床、生物和生化缓解）患者的 sc-IFX 浓度更高 [7]。该研究还确定了 20 μg/mL 的 sc-IFX 浓度与深度缓解相关 [7]。一项多中心观察性研究纳入了 220 例从 iv-IFX 转为 sc-IFX 的临床缓解期 IBD 患者，结果显示，第 12 周时临床和生化缓解联合缓解的患者的 sc-IFX 浓度显著升高 [8]。根据 ROC 分析，临床和生化缓解的最佳 sc-IFX 浓度临界值为第 12 周的 12.2 和 第 52 周的 13.2 μg/mL [8]。这些 sc-IFX 浓度临界值似乎比先前确定的 iv-IFX 浓度临界值高得多 [1， 2]。这与关键性 CT-P13 RCT 相似，其中第 22 周的平均 （SD） 谷 sc-IFX 浓度为 21.5 （9.9） μg/mL，而静脉组为 2.9 （2.6） μg/mL [9]。

总之，目前的研究提供了进一步的证据，表明较高的 sc-IFX 浓度与 IBD 患者的良好结果相关。这表明 TDM 对 sc-IFX 的重要性可能与对 iv-IFX 一样重要。然而，sc-IFX 的治疗阈值似乎比我们习惯的 iv-IFX（通常为 5-10 μg/mL）高得多（可能为 15-20 μg/mL 甚至更高）。需要进一步的研究来证实这些结果以及 TDM 与 sc-IFX 的作用。