Ma Christopher, Huang Vivian, Fedorak Darryl K, Kroeker Karen I, Dieleman Levinus A, Halloran Brendan P, Fedorak Richard N
Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
J Crohns Colitis. 2014 Nov;8(11):1454-63. doi: 10.1016/j.crohns.2014.05.007. Epub 2014 Jun 16.
The efficacy of anti-tumor necrosis factor alpha agents in maintaining remission in Crohn's disease may wane over time, leading to secondary loss of response that can often be overcome with dose escalation. Comparison of secondary loss of response of adalimumab and infliximab during long-term treatment of CD in a real-life IBD clinic has not been previously evaluated.
A retrospective cohort study was conducted evaluating outpatients with CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and who experienced a secondary loss of response. All infliximab-treated patients were anti-TNF naïve. Adalimumab-treated patients were stratified by prior anti-TNF exposure. Kaplan-Meier analysis was conducted to compare time to loss of response.
218 CD patients met inclusion criteria (117 infliximab, 101 adalimumab). Median follow-up duration was 170.0weeks for infliximab and 122.0weeks for adalimumab (p=0.61). The proportion of patients with secondary loss of response was similar for infliximab-treated - 51.3% (60/117) compared to adalimumab patients naïve to anti-TNF therapy - 60.5% (23/38) (p=0.32), and adalimumab patients with prior anti-TNF exposure - 65.1% (41/63) (p=0.08). Median time to secondary loss of response was longer for infliximab patients (99.3wk, IQR 55.7-168.5) compared to both adalimumab patients naïve to anti-TNF therapy (58.9wk, IQR 29.0-85.7) (p=0.03), and adalimumab patients with prior anti-TNF exposure (52.7wk, IQR 20.1-85.0) (p<0.001).
Over 50% of CD patients treated with infliximab and adalimumab develop secondary loss of response. Time to loss of response was shorter in patients treated with adalimumab compared to those treated with infliximab. Prior anti-TNF exposure further accelerated time to loss of response.
抗肿瘤坏死因子α制剂在维持克罗恩病缓解方面的疗效可能会随时间减弱,导致继发性反应丧失,而这通常可通过增加剂量来克服。此前尚未评估在现实生活中的炎症性肠病诊所对克罗恩病患者进行长期治疗期间,阿达木单抗和英夫利昔单抗继发性反应丧失的情况。
开展一项回顾性队列研究,评估200至2013年期间接受阿达木单抗或英夫利昔单抗维持治疗方案且出现继发性反应丧失的克罗恩病门诊患者。所有接受英夫利昔单抗治疗的患者之前均未使用过抗TNF药物。接受阿达木单抗治疗的患者根据之前是否接触过抗TNF药物进行分层。采用Kaplan-Meier分析比较反应丧失时间。
218例克罗恩病患者符合纳入标准(117例接受英夫利昔单抗治疗,101例接受阿达木单抗治疗)。英夫利昔单抗组的中位随访时间为170.0周,阿达木单抗组为122.0周(p = 0.61)。接受英夫利昔单抗治疗的患者继发性反应丧失的比例为51.3%(60/117),与未接受过抗TNF治疗的阿达木单抗患者的60.5%(23/38)(p = 0.32)以及之前接受过抗TNF治疗的阿达木单抗患者的65.1%(41/63)(p = 0.08)相似。与未接受过抗TNF治疗的阿达木单抗患者(58.9周,四分位间距29.0 - 85.7)(p = 0.03)以及之前接受过抗TNF治疗的阿达木单抗患者(52.7周,四分位间距20.1 - 85.0)(p < 0.001)相比,接受英夫利昔单抗治疗的患者继发性反应丧失的中位时间更长(99.3周,四分位间距55.7 - 168.5)。
超过50%接受英夫利昔单抗和阿达木单抗治疗的克罗恩病患者出现继发性反应丧失。与接受英夫利昔单抗治疗的患者相比,接受阿达木单抗治疗的患者反应丧失时间更短。之前接触过抗TNF药物会进一步加速反应丧失时间。