*Pediatric Inflammatory Bowel Disease Center, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts; †Boston Children's Hospital Clinical Research Center, Boston, Massachusetts; and ‡Prometheus Laboratories Inc., San Diego, California.
Inflamm Bowel Dis. 2015 Feb;21(2):307-14. doi: 10.1097/MIB.0000000000000284.
Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited.
We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded.
Assays were performed on 134 subjects currently receiving infliximab (85 male; mean age, 17.3 ± 4.3 years; 114 Crohn's disease and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years: median 2.0 (interquartile range [1.1-4.3]) years. Twenty-seven of 134 (20%) patients had ATI ≥5 U/mL. Of patients with ATI ≥5 U/mL, 59% had infliximab levels <5 μg/mL, compared with 14% of patients with ATI <5 U/mL (P < 0.001). Ten (7%) patients (9 Crohn's disease, 1 ulcerative colitis) underwent bowel resections after beginning infliximab infusions. Sixty percent who underwent surgery had ATI ≥12 U/mL; in contrast, only 8% of patients who did not undergo surgery had ATI ≥12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%) patients were receiving combination therapy, compared with 84 (63%) on infliximab alone. Combination therapy at the time of serum sampling did not correlate with either increase infliximab levels or lower ATI compared with infliximab monotherapy. However, prior immunomodulator use was associated with lower antibody levels (P = 0.007).
ATI correlates with reduction in infliximab level and a higher risk of surgery in patients with inflammatory bowel disease.
成人研究表明，英夫利昔单抗（ATI）抗体与炎症性肠病的应答丧失相关，但儿科数据有限。
我们对 134 例接受英夫利昔单抗治疗的儿科和年轻成年患者的英夫利昔单抗谷浓度和 ATI 进行了横断面研究。在获得血清的同时记录了人口统计学资料、疾病表型、英夫利昔单抗治疗时间、联合治疗（甲氨蝶呤或 6-巯基嘌呤联合英夫利昔单抗）和手术情况。
对 134 例目前正在接受英夫利昔单抗治疗的患者（85 例男性；平均年龄 17.3±4.3 岁；114 例克罗恩病和 20 例溃疡性结肠炎）进行了检测。英夫利昔单抗的使用时间从 12 天到 12 年不等：中位数为 2.0（四分位距 [1.1-4.3]）年。134 例患者中有 27 例（20%）的 ATI≥5 U/mL。ATI≥5 U/mL 的患者中，59%的英夫利昔单抗水平<5μg/mL，而 ATI<5 U/mL 的患者中，这一比例为 14%（P<0.001）。10 例（9 例克罗恩病，1 例溃疡性结肠炎）患者在开始英夫利昔单抗输注后接受了肠切除术。接受手术的患者中有 60%的 ATI≥12 U/mL；相比之下，未接受手术的患者中只有 8%的 ATI≥12 U/mL（P=0.01）。在采集血清样本时，50 例（37%）患者正在接受联合治疗，而单独接受英夫利昔单抗治疗的患者为 84 例（63%）。与英夫利昔单抗单药治疗相比，在采集血清样本时联合治疗与增加英夫利昔单抗水平或降低 ATI 无关。然而，先前使用免疫调节剂与较低的抗体水平相关（P=0.007）。
ATI 与炎症性肠病患者英夫利昔单抗水平降低和手术风险增加相关。
