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克罗恩病患者长期英夫利昔单抗治疗的预后因素:一项为期20年的单中心经验

Prognostic factors for long-term infliximab treatment in Crohn's disease patients: a 20-year single centre experience.

作者信息

Billiet T, Cleynen I, Ballet V, Ferrante M, Van Assche G, Gils A, Vermeire S

机构信息

Department of Clinical and Experimental Medicine, Translational Research Center for GastroIntestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

出版信息

Aliment Pharmacol Ther. 2016 Oct;44(7):673-83. doi: 10.1111/apt.13754. Epub 2016 Aug 9.

Abstract

BACKGROUND

The long-term efficacy of infliximab in patients with Crohn's disease is suboptimal.

AIM

To study prognostic factors for real-life long-term effcacy of infliximab in Crohn's disease.

METHODS

All consecutive Crohn's disease patients treated with infliximab at a tertiary centre were retrospectively analysed. Only patients who received scheduled infliximab maintenance treatment were considered. Patient- and disease-related factors were used to identify independent predictors of infliximab failure-free survival using Cox proportional hazards regression.

RESULTS

Of 1031 patients with Crohn's disease, 261 were eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4-4.7] years, and 65 (24.9%) patients experienced infliximab failure. Estimated 5-year infliximab failure-free survival was 65.9% (95% CI 58.3-73.5). Multivariate Cox regression identified disease duration ≥1 year (HR 2.5 (95% CI 1.2-5.2), P = 0.02), L1 disease location [HR 2.0 (1.1-3.5), P = 0.02], prior anti-TNF use [HR 2.3 (1.1-4.8), P = 0.03], haemoglobin <13.5 g/dL [HR 2.3 (1.2-4.4), P = 0.02], not using therapeutic drug monitoring [HR 8.0 (4.1-15.6), P = 1 × 10(-9) ], and first dose optimisation within first year [HR 3.7 (2.1-6.6), P = 5 × 10(-6) ] as independent predictors of infliximab failure-free survival. Stratifying patients into risk groups resulted in estimated 3-year infliximab failure-free survival rates ranging from 95.3% (94.2-96.4) to 26.3% (8.6-44.0) depending on the number of risk factors (P = 8 × 10(-13) ).

CONCLUSIONS

This study identified several easy to obtain predictors of infliximab failure in patients with Crohn's disease, and these are in line with previous reports. Those with a high-risk profile for infliximab failure in whom infliximab initiation is considered, should be treated as early as possible making use of therapeutic drug monitoring.

摘要

背景

英夫利昔单抗治疗克罗恩病患者的长期疗效欠佳。

目的

研究英夫利昔单抗治疗克罗恩病实际长期疗效的预后因素。

方法

对在一家三级中心接受英夫利昔单抗治疗的所有连续性克罗恩病患者进行回顾性分析。仅纳入接受英夫利昔单抗定期维持治疗的患者。使用患者和疾病相关因素,通过Cox比例风险回归确定英夫利昔单抗无失败生存的独立预测因素。

结果

1031例克罗恩病患者中,261例符合纳入标准。英夫利昔单抗治疗的中位时间为2.4[四分位间距1.4 - 4.7]年,65例(24.9%)患者出现英夫利昔单抗治疗失败。估计5年英夫利昔单抗无失败生存率为65.9%(95%CI 58.3 - 73.5)。多因素Cox回归确定疾病病程≥1年(HR 2.5(95%CI 1.2 - 5.2),P = 0.02)、L1疾病部位[HR 2.0(1.1 - 3.5),P = 0.02]、既往使用抗TNF药物[HR 2.3(1.1 - 4.8),P = 0.03]、血红蛋白<13.5 g/dL[HR 2.3(1.2 - 4.4),P = 0.02]、未使用治疗药物监测[HR 8.0(4.1 - 15.6),P = 1×10⁻⁹]以及在第一年内进行首剂优化[HR 3.7(2.1 - 6.6),P = 5×10⁻⁶]为英夫利昔单抗无失败生存的独立预测因素。根据风险因素数量将患者分层,估计3年英夫利昔单抗无失败生存率在95.3%(94.2 - 96.4)至26.3%(8.6 - 44.0)之间(P = 8×10⁻¹³)。

结论

本研究确定了克罗恩病患者中几个易于获得的英夫利昔单抗治疗失败预测因素,与既往报道一致。对于考虑开始使用英夫利昔单抗但具有高失败风险的患者,应尽早利用治疗药物监测进行治疗。

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