Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Rainbow Babies and Children's Hospital.
Case Western Reserve University School of Medicine.
Eur J Gastroenterol Hepatol. 2019 Oct;31(10):1228-1233. doi: 10.1097/MEG.0000000000001538.
Loss of response in pediatric inflammatory bowel disease patients treated with biologic medications can be due to development of anti-drug antibodies. Natural history of anti-drug antibodies development has not been well described in pediatric inflammatory bowel disease. The primary aim of this study was to describe a single-center experience for the temporal onset of anti-drug antibodies detection.
We performed a retrospective, single-center chart review of pediatric inflammatory bowel disease patients at the Division of Pediatric Gastroenterology, Hepatology, and Nutrition at Rainbow Babies and Children's Hospital from 2010 to 2015. Patients were treated with infliximab or adalimumab and had at least two evaluations for anti-drug antibodies with the homogenous mobility shift assay. Demographics, laboratory and medication data, and clinical disease activity were collected.
A total of 75 subjects are included in the analysis. Eighty-one percent of subjects were treated with infliximab. Eleven subjects developed anti-drug antibodies; average time to anti-drug antibodies detection was 13.2 ± 7.3 months. Longer duration of inflammatory bowel disease, L1 location in Crohn's disease, and not having immunomodulatory therapy before biologic was associated with higher risk of antibody detection. Antibody detection occurred more frequently with infliximab vs. adalimumab. Time-to-antibody detection for infliximab and adalimumab was 14.83 and 23.48 months, respectively.
Chances of anti-drug antibodies detection in the infliximab group were higher than the adalimumab group. Time-to-antibody detection was 8.65 months longer in patients who received adalimumab when compared to infliximab. These results may have implications for long-term therapy and help guide use of concomitant immunomodulators.
接受生物药物治疗的儿科炎症性肠病患者的反应丧失可能是由于抗药物抗体的产生。儿科炎症性肠病患者抗药物抗体发展的自然史尚未得到很好的描述。本研究的主要目的是描述单中心检测抗药物抗体的时间发生情况。
我们对 2010 年至 2015 年在彩虹婴儿和儿童医院儿科胃肠病学、肝脏病学和营养学系接受英夫利昔单抗或阿达木单抗治疗的儿科炎症性肠病患者进行了回顾性、单中心图表回顾。至少有两次使用同型迁移率变动检测评估抗药物抗体。收集了人口统计学、实验室和药物数据以及临床疾病活动数据。
共分析了 75 名受试者。81%的受试者接受英夫利昔单抗治疗。11 名患者产生了抗药物抗体;抗药物抗体检测的平均时间为 13.2±7.3 个月。炎症性肠病的持续时间较长、克罗恩病的 L1 位置以及在使用生物制剂之前没有免疫调节治疗与抗体检测的风险较高相关。与阿达木单抗相比,英夫利昔单抗更常检测到抗体。英夫利昔单抗和阿达木单抗的抗体检测时间分别为 14.83 和 23.48 个月。
英夫利昔单抗组检测到抗药物抗体的几率高于阿达木单抗组。与英夫利昔单抗相比,接受阿达木单抗的患者的抗体检测时间延长了 8.65 个月。这些结果可能对长期治疗有影响,并有助于指导同时使用免疫调节剂。