Abstract：
OBJECTIVE: Multiple studies in patients with Crohn\'s disease (CD) treated with anti-tumor necrosis factor alpha agents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated infliximab administration during induction resulted in improved outcomes.
METHODS: This retrospective study included CD patients aged 5-17.9 years that were treated with infliximab. We compared outcomes of patients treated during induction with 5-8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of infliximab. Primary outcome was steroid-free clinical remission by Week 52.
RESULTS: Sixty-eight patients were included, of whom seven discontinued infliximab before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at infliximab initiation. Despite receiving significantly more infliximab, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn\'s disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5-20] vs. 5 [0-15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough infliximab levels by Week 52.
CONCLUSIONS: Accelerated infliximab dosing during induction did not result in improved outcomes up to 12 months follow-up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied.
METHODS: This retrospective study included CD patients aged 5-17.9 years that were treated with infliximab. We compared outcomes of patients treated during induction with 5-8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of infliximab. Primary outcome was steroid-free clinical remission by Week 52.
RESULTS: Sixty-eight patients were included, of whom seven discontinued infliximab before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at infliximab initiation. Despite receiving significantly more infliximab, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn\'s disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5-20] vs. 5 [0-15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough infliximab levels by Week 52.
CONCLUSIONS: Accelerated infliximab dosing during induction did not result in improved outcomes up to 12 months follow-up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied.
摘要：
目的：在接受抗肿瘤坏死因子α药物治疗的克罗恩病（CD）患者中的多项研究表明，在维持阶段进行主动治疗药物监测（TDM）可改善预后。我们旨在评估诱导过程中加速英夫利昔单抗给药是否导致改善的结果。
方法：这项回顾性研究包括5-17.9岁接受英夫利昔单抗治疗的CD患者。我们比较了在第0、2、6和14周（第1组）以5-8mg/kg剂量诱导治疗的患者的结果。英夫利昔单抗的加速给药（≥8mg/kg和/或>4次输注至第14周，第2组）。主要结果是到第52周时无类固醇临床缓解。
结果：纳入68例患者，其中7人因输液反应在第14周之前停用英夫利昔单抗，免疫原性失败，或主要无反应。第1组（n=25）和第2组（n=36）的比较显示相似的临床特征，以及炎症标志物，在英夫利昔单抗开始。尽管接受了明显更多的英夫利昔单抗，到第14周时达到较高的低谷水平（10.3±1.2与3.3±0.7，p<0.001)，与第1组相比，第2组的儿童克罗恩病活动指数（PCDAI）中位数略高（14[5-20]与5[0-15],p=0.02)。然而,在第26周和第52周,两组间PCDAI和炎症标志物具有可比性.此外，到第52周时,两组中约70%的英夫利昔单抗水平达到理想的谷值.
结论：在诱导过程中加速英夫利昔单抗给药并不能改善长达12个月的随访结果。需要进行前瞻性研究以确定应用主动TDM的确切时机。
方法：这项回顾性研究包括5-17.9岁接受英夫利昔单抗治疗的CD患者。我们比较了在第0、2、6和14周（第1组）以5-8mg/kg剂量诱导治疗的患者的结果。英夫利昔单抗的加速给药（≥8mg/kg和/或>4次输注至第14周，第2组）。主要结果是到第52周时无类固醇临床缓解。
结果：纳入68例患者，其中7人因输液反应在第14周之前停用英夫利昔单抗，免疫原性失败，或主要无反应。第1组（n=25）和第2组（n=36）的比较显示相似的临床特征，以及炎症标志物，在英夫利昔单抗开始。尽管接受了明显更多的英夫利昔单抗，到第14周时达到较高的低谷水平（10.3±1.2与3.3±0.7，p<0.001)，与第1组相比，第2组的儿童克罗恩病活动指数（PCDAI）中位数略高（14[5-20]与5[0-15],p=0.02)。然而,在第26周和第52周,两组间PCDAI和炎症标志物具有可比性.此外，到第52周时,两组中约70%的英夫利昔单抗水平达到理想的谷值.
结论：在诱导过程中加速英夫利昔单抗给药并不能改善长达12个月的随访结果。需要进行前瞻性研究以确定应用主动TDM的确切时机。
