Ben-Horin S, Chowers Y, Ungar B, Kopylov U, Loebstein R, Weiss B, Eliakim R, Del Tedesco E, Paul S, Roblin X
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.
Aliment Pharmacol Ther. 2015 Aug;42(3):356-64. doi: 10.1111/apt.13268. Epub 2015 Jun 1.
Low drug levels are associated with emerging loss of response to anti-TNF. However, this may not be the case in patients with long-term remission.
To investigate the outcome of anti-TNF discontinuation in patients with long-term remission and incidental undetectable drug levels.
A retrospective cohort study examining the duration of relapse-free survival in IBD patients in remission who discontinued infliximab or adalimumab having undetectable drug levels.
Forty eight patients who discontinued anti-TNF while in remission and had available drug levels were identified in two centres in France and Israel (infliximab-treated 35, adalimumab-13, Crohn's disease 30, ulcerative colitis 18, mean treatment duration of 22.7 ± 12.4 months). Endoscopy/MRE before stopping showed absence of active inflammation in 40/42 (95%) of evaluated patients, while inflammatory biomarkers (CRP and/or Calprotectin) were completely normal in only 31/48 (65%) of patients. During 12 months median follow-up, relapse occurred in 16/20 (80%) of patients who stopped anti-TNF while having measurable drug levels compared with 9/28 (32%) of patients who had undetectable drug levels (OR: 8.4, 95% CI: 2.2-32, P = 0.002). Relapse-free survival after anti-TNF cessation was significantly longer in patients with absent drug compared to those with detectable drug (P < 0.001, log rank test). On multivariate analysis, a patient's decision to stop therapy was weakly associated and abnormal inflammatory biomarkers and detectable drug levels were both strongly and independently associated with a higher risk of relapse after drug discontinuation.
Incidental finding of undetectable anti-TNF drug levels in patients with stable long-term deep remission may identify a subset of patients whose clinical remission is no longer dependent on anti-TNF treatment.
药物水平低与抗TNF治疗反应的逐渐丧失有关。然而，长期缓解的患者可能并非如此。
研究长期缓解且偶然出现药物水平不可测的患者停用抗TNF的结果。
一项回顾性队列研究，考察缓解期停用英夫利昔单抗或阿达木单抗且药物水平不可测的炎症性肠病（IBD）患者的无复发生存期。
在法国和以色列的两个中心，共确定了48例在缓解期停用抗TNF且有可用药物水平的患者（英夫利昔单抗治疗35例，阿达木单抗治疗13例；克罗恩病30例，溃疡性结肠炎18例；平均治疗持续时间22.7±12.4个月）。停药前的内镜检查/磁共振肠造影（MRE）显示，42例接受评估的患者中有40例（95%）无活动性炎症，而仅31/48例（65%）患者的炎症生物标志物（CRP和/或钙卫蛋白）完全正常。在12个月的中位随访期内，药物水平可测时停用抗TNF的患者中，16/20例（80%）复发，而药物水平不可测的患者中9/28例（32%）复发（比值比：8.4，95%置信区间：2.2 -
