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英夫利昔单抗谷浓度可能预测克罗恩病患者对英夫利昔单抗的持续应答。

Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease.

机构信息

1st Faculty of Medicine, Charles University in Prague, Czech Republic.

出版信息

J Crohns Colitis. 2013 Oct;7(9):736-43. doi: 10.1016/j.crohns.2012.10.019. Epub 2012 Nov 29.

Abstract

BACKGROUND AND AIMS

Over 10% of Crohn's disease (CD) patients annually lose response to infliximab. Infliximab trough levels (TL), concomitant immunosuppressants and endoscopic healing were proposed as predictors of favourable infliximab outcome. We assessed infliximab TL measured after induction therapy as predictors of sustained clinical response. Furthermore, we tried to identify other predictors of long-term benefit of infliximab therapy.

METHODS

We included CD patients treated with infliximab between October 2007 and March 2010 who responded to 3-dose induction followed by maintenance therapy and in whom blood samples taken at treatment week 14 or 22 were available in blood bank. Sustained response to infliximab was defined as absence of treatment failure due to loss of response or drug intolerance.

RESULTS

Eighty four patients were included. Sustained response to infliximab was observed in 47 (56%) patients during a median follow-up of 25 months (14-37). Infliximab TL>3μg/ml were associated with a decreased risk of treatment failure (HR 0.34; 95% CI: 0.16-0.75), whereas the presence of antibodies against infliximab and need for corticosteroids increased this risk (HR 4.34; 95% CI: 1.51-12.5 and HR 2.49, 95% CI: 1.08-5.73, respectively). No impact of concomitant thiopurines was observed, although patients receiving thiopurines had higher infliximab TL than those without immunomodulators (5.51 vs. 0.71μg/ml; p=0.01).

CONCLUSION

During a median follow up of 2 years sustained response to infliximab was observed in slightly more than half of CD patients. Infliximab TL>3μg/ml at the start of maintenance regime were predicative of sustained response to infliximab.

摘要

背景与目的

超过 10%的克罗恩病(CD)患者每年对英夫利昔单抗失去应答。英夫利昔单抗谷浓度(TL)、同时使用的免疫抑制剂和内镜愈合被认为是英夫利昔单抗治疗效果良好的预测指标。我们评估了诱导治疗后测定的英夫利昔单抗 TL 作为持续临床应答的预测指标。此外,我们试图确定英夫利昔单抗治疗长期获益的其他预测指标。

方法

我们纳入了 2007 年 10 月至 2010 年 3 月期间接受英夫利昔单抗治疗的 CD 患者,这些患者对 3 剂量诱导治疗后进行维持治疗,并且在治疗第 14 或 22 周时在血库中可获得血液样本。英夫利昔单抗的持续应答定义为由于无应答或药物不耐受而无治疗失败。

结果

共纳入 84 例患者。在中位随访 25 个月(14-37 个月)期间,47 例(56%)患者对英夫利昔单抗持续应答。英夫利昔单抗 TL>3μg/ml 与治疗失败风险降低相关(HR 0.34;95%CI:0.16-0.75),而抗英夫利昔单抗抗体的存在和需要使用皮质类固醇增加了这种风险(HR 4.34;95%CI:1.51-12.5 和 HR 2.49;95%CI:1.08-5.73)。同时使用硫唑嘌呤没有影响,尽管接受硫唑嘌呤的患者英夫利昔单抗 TL 高于未使用免疫调节剂的患者(5.51 vs. 0.71μg/ml;p=0.01)。

结论

在中位随访 2 年期间,略超过一半的 CD 患者对英夫利昔单抗持续应答。维持治疗开始时英夫利昔单抗 TL>3μg/ml 预测英夫利昔单抗持续应答。

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