Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
J Pediatr Gastroenterol Nutr. 2024 Sep;79(3):564-572. doi: 10.1002/jpn3.12307. Epub 2024 Jul 9.
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 (IFX) administration during induction resulted in improved outcomes.
This retrospective study included CD patients aged 5-17.9 years that were treated with IFX. 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 IFX. Primary outcome was steroid-free clinical remission by Week 52.
Sixty-eight patients were included, of whom seven discontinued IFX 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 IFX initiation. Despite receiving significantly more IFX, 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 IFX levels by Week 52.
Accelerated IFX 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.
多项针对接受肿瘤坏死因子 α 拮抗剂治疗的克罗恩病（CD）患者的研究表明，在维持期进行主动治疗药物监测（TDM）可改善治疗结果。本研究旨在评估诱导期加速（IFX）给药是否可改善结局。
这是一项回顾性研究，纳入了接受 IFX 治疗的 5-17.9 岁 CD 患者。我们比较了第 0、2、6 和 14 周时给予 5-8mg/kg 剂量（第 1 组）与 IFX 加速给药（≥8mg/kg 和/或第 14 周前输注次数>4 次，第 2 组）的患者结局。主要结局为第 52 周时无激素的临床缓解。
共纳入 68 例患者，其中 7 例在第 14 周前因输注反应、免疫原性失败或原发性无应答而停止 IFX 治疗。第 1 组（n=25）和第 2 组（n=36）的患者在 IFX 起始时具有相似的临床特征和炎症标志物。尽管第 2 组接受了更多的 IFX，且在第 14 周时达到了更高的谷浓度（10.3±1.2 比 3.3±0.7，p<0.001），但第 2 组的中位数小儿克罗恩病活动指数（PCDAI）仍略高于第 1 组（14[5-20]比 5[0-15]，p=0.02）。然而，在第 26 和 52 周时，两组间 PCDAI 和炎症标志物均无差异。此外，两组中约 70%的患者在第 52 周时达到了理想的 IFX 谷浓度。
在诱导期加速 IFX 给药并未改善 12 个月随访时的结局。需要前瞻性研究来确定主动 TDM 应应用的确切时间。
