Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
Am J Gastroenterol. 2010 May;105(5):1133-9. doi: 10.1038/ajg.2010.9. Epub 2010 Feb 9.
Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab concentrations are associated with decreased duration of response. We evaluated the clinical utility of measuring HACA and infliximab concentrations.
The medical records of patients with inflammatory bowel disease (IBD) who had HACA and infliximab concentrations measured were reviewed to determine whether the result affected clinical management.
One hundred fifty-five patients had HACA and infliximab concentrations measured. The main indications for testing were loss of response to infliximab (49%), partial response after initiation of infliximab (22%), and possible autoimmune/delayed hypersensitivity reaction (10%). HACAs were identified in 35 patients (23%) and therapeutic infliximab concentrations in 51 patients (33%). Of 177 tests assessed, the results impacted treatment decisions in 73%. In HACA-positive patients, change to another anti-tumor necrosis factor (TNF) agent was associated with a complete or partial response in 92% of patients, whereas dose escalation had a response of 17%. In patients with subtherapeutic infliximab concentrations, dose escalation was associated with complete or partial clinical response in 86% of patients whereas changing to another anti-TNF agent had a response of 33%. Patients with clinical symptoms and therapeutic infliximab concentrations were continued at the same dose 76% of the time and had no evidence of active inflammation by endoscopic/radiographic assessment 62% of the time.
Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.
人抗嵌合抗体（HACA）和低于治疗剂量的英夫利昔单抗浓度与应答持续时间缩短相关。我们评估了测定 HACA 和英夫利昔单抗浓度的临床实用性。
回顾性分析了检测 HACA 和英夫利昔单抗浓度的炎症性肠病（IBD）患者的病历，以确定检测结果是否影响临床管理。
155 例患者检测了 HACA 和英夫利昔单抗浓度。检测的主要指征是英夫利昔单抗应答丧失（49%）、英夫利昔单抗起始后部分应答（22%）和可能的自身免疫/迟发性超敏反应（10%）。35 例患者（23%）检测到 HACA，51 例患者（33%）检测到治疗性英夫利昔单抗浓度。在评估的 177 次检测中，有 73%的检测结果影响了治疗决策。在 HACA 阳性患者中，92%的患者改用另一种抗 TNF 药物后出现完全或部分应答，而剂量增加的应答率为 17%。在英夫利昔单抗浓度低于治疗范围的患者中，剂量增加与 86%的患者完全或部分临床应答相关，而改用另一种抗 TNF 药物的应答率为 33%。76%的时间，有临床症状和治疗性英夫利昔单抗浓度的患者继续使用相同剂量，62%的时间内镜/影像学评估无活动炎症证据。
测定 HACA 和英夫利昔单抗浓度可影响治疗管理，具有临床实用性。在有 HACA 的患者中增加英夫利昔单抗剂量无效，而在英夫利昔单抗浓度低于治疗范围的患者中，这一策略可能是改用另一种抗 TNF 药物的良好替代方案。
