Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: A randomized controlled trial
Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: A randomized controlled trial
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DOI：
10.1053/gast.2003.50145
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发表时间：
2003-04-01
期刊：
影响因子：
29.4
通讯作者：
Michetti, P
中科院分区：
文献类型：
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作者：
Farrell, RJ;Alsahli, M;Michetti, P
背景与目的：我们评估了英夫利昔单抗抗体（ATI）与英夫利昔单抗后反应丧失之间的关系，并在一项随机试验中研究了静脉注射氢化可的松预用药是否可以减少ATI。方法：最初，我们前瞻性地评估了53例连续接受199次英夫利昔单抗（5mg /kg）输注的克罗恩病患者的临床反应、不良事件和ATI水平。随后，80名克罗恩病患者在第一次和随后的英夫利昔单抗输注前随机接受静脉注射200mg氢化可的松或安慰剂。主要终点是第16周时ATI中位水平的降低。分析的目的是治疗。结果：53例患者中有19例（36%）发生ATI，其中7例患者均出现严重输液反应（ATI中位数为19.6马克杯/毫升）。15例失去初始应答的患者中有11例（73%）是ATI阳性，而21例持续应答者中没有ATI阳性（8.9 vs. 0.7 mug/mL, P < 0.0001）。在第一次输注后8周内进行第二次输注（OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007）或同时使用免疫抑制剂（OR, 0.19; 95% CI, 0.04-1.03; P = 0.007）可显著减少ATI的形成。在安慰剂对照试验中，在氢化可的松治疗的患者中，ATI水平在第16周时较低（1.6 vs. 3.4马克/毫升，P = 0.02）， 26%的氢化可的松治疗的患者发生ATI，而安慰剂治疗的患者为42%，P = 0.06。结论。英夫利昔单抗后初始反应和输液反应的丧失与ATI的形成和水平密切相关。在第一次免疫抑制剂治疗后8周内进行第二次输注，并同时进行免疫抑制剂治疗，可显著减少ATI的形成。静脉注射氢化可的松预用药可显著降低ATI水平，但不能消除ATI的形成或输液反应。
Background & Aims: We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. Methods: Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. Results: Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 mug/mL. Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 mug/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 mug/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. Conclusions. Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions.