Objective To evaluate the clinical relevance of antidrug antibodies (ADAs) measured using a drug-tolerant assay in a post hoc analysis of the Trough Concentration (TC) Adapted Infliximab Treatment (TAXIT) randomised controlled trial. Design ADA in serum samples (n=221) of 76 patients enrolled in TAXIT, who presented with an infliximab TC <3 µg/mL at screening, were reanalysed after optimisation and at the end of the study using a drug-tolerant ADA assay. Patients underwent dose escalation to achieve therapeutic TCs between 3 µg/mL and 7 µg/mL prior to randomisation. Patients were grouped into quartiles (Q1–4) according to ADA concentration at screening. Results Using a drug-tolerant assay, the immunogenicity detection rate increased from 21% (drug-sensitive assay) to 63% at screening, from 0% to 51% after optimisation and from 3% to 42% at the end of TAXIT. Patients in ADA Q4 required a higher cumulative infliximab dose (2390 (880–2998) mg) to achieve target TCs, resulting in a higher drug cost (€10 712 (4120–13 596)) compared with ADA-negative patients (€2060 (1648–3296)) and patients in ADA Q1/Q2 (€2060 (1648–4120)/€2060 (1751–3296), p<0.001). However, all but one patient belonging to ADA Q4 were also ADA-positive using a drug-sensitive assay. Conclusions Upon dose intensification, low concentration ADAs, not detectable using a drug-sensitive assay, disappear in more than half of the patients over time and are clinically non-relevant. In contrast, high concentration ADAs which are typically also detected in a drug-sensitive assay, persist over time and necessitate a higher cumulative dose and drug cost. In the latter group, proactive drug switching may be more cost-efficient. Clinical Trials Register 2011-002061-38; Post-results.

中文翻译：

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用耐药性检测检测抗英夫利昔单抗抗体的临床相关性：TAXIT 试验的事后分析

目的 在谷浓度 (TC) 适应性英夫利昔单抗治疗 (TAXIT) 随机对照试验的事后分析中，评估使用耐药性测定法测量的抗药抗体 (ADA) 的临床相关性。纳入 TAXIT 的 76 名患者的血清样本 (n=221) 中的设计 ADA，在筛选时呈现英夫利昔单抗 TC <3 µg/mL，在优化后和在研究结束时使用耐药性 ADA 测定重新分析。在随机化之前，患者经历了剂量递增以达到 3 µg/mL 至 7 µg/mL 之间的治疗性 TC。根据筛选时的 ADA 浓度将患者分为四分位数 (Q1-4)。结果使用耐药性检测，免疫原性检测率从筛选时的 21%（药物敏感检测）增加到 63%，优化后从 0% 到 51%，在 TAXIT 结束时从 3% 到 42%。与 ADA 阴性患者（2060 欧元）相比，ADA Q4 中的患者需要更高的英夫利昔单抗累积剂量（2390（880-2998）mg）才能达到目标 TC，导致更高的药物成本（10712 欧元（4120-13596）） (1648-3296)) 和 ADA Q1/Q2 患者（2060 欧元（1648-4120）/2060 欧元（1751-3296），p<0.001）。然而，除一名属于 ADA Q4 的患者外，其他所有患者也使用药物敏感测定法呈 ADA 阳性。结论 在剂量强化后，使用药物敏感试验无法检测到的低浓度 ADA 会随着时间的推移在超过一半的患者中消失，并且在临床上不相关。相比之下，通常也在药物敏感测定中检测到的高浓度 ADAs 会随着时间的推移持续存在，并且需要更高的累积剂量和药物成本。在后一组中，主动换药可能更具成本效益。临床试验注册 2011-002061-38；后结果。