Supplementary Material for: Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus

Background: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. Methods: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. Results: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn’s disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. Conclusion: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.背景：接受抗肿瘤坏死因子（TNF）类药物治疗的炎症性肠病（IBD）患者常出现应答丧失情况。治疗药物监测（TDM）与抗药物抗体检测在该临床场景中的应用日益广泛。 方法：为就抗TNF药物应答丧失场景下的治疗药物监测应用达成共识，我们采用德尔菲法流程开展投票，随后由来自欧洲瑞士的8名炎症性肠病专科医师组成专家小组进行讨论。基于专家意见与现有文献，研究采用1（完全不赞同）至4（完全赞同）的连续李克特量表对各项声明进行评分。 结果：专家小组就以下声明达成共识：（1）克罗恩病与溃疡性结肠炎患者的应答丧失均与药物浓度不足相关；（2）检测药物浓度的最佳时机为下次给药前（即谷浓度），不同抗TNF药物的浓度阈值各异：英夫利昔单抗为5 μg/mL、阿达木单抗为8 μg/mL、赛妥珠单抗为10 μg/mL；（3）抗药物抗体可预测应答丧失；（4）抗药物抗体滴度与药物谷浓度是治疗流程中的关键决定因素。现有关于非抗TNF类生物制剂的数据过于有限，无法提出相关推荐意见。 结论：由8名炎症性肠病专科医师组成的专家小组通过德尔菲法达成的共识显示，治疗药物监测与抗药物抗体滴度检测在抗TNF药物应答丧失的临床场景中具有应用价值。最佳临界浓度因抗TNF药物类型而异，此类数值在临床决策过程中至关重要。目前仍需开展更多研究，以明确此类检测在非抗TNF类生物制剂中的应用价值。