预防先前硫嘌呤类药物治疗失败的克罗恩病患者对英夫利昔单抗产生抗药物抗体。
Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines.
机构信息
Department of Internal Medicine H, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
出版信息
Clin Gastroenterol Hepatol. 2017 Jan;15(1):69-75. doi: 10.1016/j.cgh.2016.06.028. Epub 2016 Jul 9.
BACKGROUND & AIMS: Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown.
METHODS
This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance.
RESULTS
Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P = .54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P = .007) and past thiopurine failures (P = .007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22-1.00] and 0.32 [95% CI, 0.11-0.93], respectively).
CONCLUSIONS
Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.
背景与目的
与英夫利昔单抗（IFX）单药治疗相比，联合硫嘌呤-英夫利昔单抗（IFX）治疗可减少抗药物抗体（ADA）的产生。既往硫嘌呤治疗的临床反应是否对 ADA 的预防有影响尚不清楚。
方法
这是一项回顾性观察性多中心研究，纳入了接受 IFX 和硫嘌呤治疗且有连续 ADA 检测的克罗恩病（CD）患者。将治疗分为既往硫嘌呤反应组、既往硫嘌呤无反应组、新联合组和 IFX 单药组。主要终点为 ADA 出现的风险。
结果
在 494 例有连续 ADA 检测的患者中，有 207 例符合最终分析条件。既往硫嘌呤反应者（19.3%）和既往硫嘌呤无反应者（16.1%）的 1 年 ADA 累积发生率相似（对数秩检验 P=0.54）。单药组中 ADA 发生率为 46.6%，与既往硫嘌呤反应者（P=0.007）和既往硫嘌呤无反应者（P=0.007）均有显著差异。与单药组相比，既往硫嘌呤反应者和既往硫嘌呤无反应者发生 ADA 的调整风险比显著降低（风险比，0.47[95%CI，0.22-1.00]和 0.32[95%CI，0.11-0.93]）。
结论
与 IFX 单药治疗相比，联合硫嘌呤-IFX 治疗 CD 患者可减少 ADA 的形成。这可能与初始硫嘌呤治疗效果无关。
Zotero 插件