Strik Anne S, Löwenberg Mark, Buskens Christianne J, B Gecse Krisztina, I Ponsioen Cyriel, Bemelman Willem A, D'Haens Geert R
a Department of Gastroenterology and Hepatology , Amsterdam UMC, University of Amsterdam , Amsterdam , Netherlands.
b Department of Surgery , Amsterdam UMC, University of Amsterdam , Amsterdam , Netherlands.
Scand J Gastroenterol. 2019 Apr;54(4):453-458. doi: 10.1080/00365521.2019.1600014. Epub 2019 Apr 28.
Anti-TNF agents are effective to treat perianal Crohn's disease (CD). Evidence suggests that Crohn's disease patients with perianal fistulas need higher infliximab (IFX) serum concentrations compared to patients without perianal CD to achieve complete disease control. Our aim was to compare anti-TNF serum concentrations between patients with actively draining and closed perianal fistulas. A retrospective survey was performed in CD patients with perianal disease treated with IFX or adalimumab (ADL). Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging. We identified 66 CD patients with a history of perianal fistulas treated with IFX ( = 47) and ADL ( = 19). Median IFX serum trough concentrations ([interquartile range]) were higher in patients with closed fistulas ( = 32) compared to patients with actively draining fistulas ( = 15): 6.0 µg/ml [5.4-6.9] versus 2.3 µg/ml [1.1-4.0], respectively ( < .001)). A similar difference was seen in patients treated with ADL: median serum concentrations were 7.4 µg/ml [6.5-10.8] in 13 patients with closed fistulas versus 4.8 µg/ml [1.7-6.2] in 6 patients with producing fistulas ( = .003). Serum concentrations of ≥5.0 µg/ml for IFX (area under the curve of 0.92; 95% CI: 0.82-1.00)) and 5.9 µg/ml for ADL (area under the curve of 0.89; 95% CI 0.71-1.00) were associated with fistula closure. Cut-off serum concentrations ≥5.0 µg/ml for IFX and ≥5.9 µg/ml for ADL were associated with perianal fistula closure. Hence, patients with producing perianal fistulas may benefit from anti-TNF dose intensification to achieve fistula closure.
抗TNF药物对治疗肛周克罗恩病（CD）有效。有证据表明，与无肛周CD的患者相比，患有肛周瘘管的克罗恩病患者需要更高的英夫利昔单抗（IFX）血清浓度才能实现疾病的完全控制。我们的目的是比较有活动性引流的肛周瘘管患者和闭合性肛周瘘管患者的抗TNF血清浓度。对接受IFX或阿达木单抗（ADL）治疗的肛周疾病CD患者进行了一项回顾性调查。瘘管闭合的定义为轻压手指时无活动性引流和/或磁共振成像显示瘘管愈合。我们确定了66例有肛周瘘管病史的CD患者，其中47例接受IFX治疗，19例接受ADL治疗。与有活动性引流瘘管的患者（n = 15）相比，闭合性瘘管患者（n = 32）的IFX血清谷浓度中位数（[四分位间距]）更高：分别为6.0μg/ml [5.4 - 6.9]和2.3μg/ml [1.1 - 4.0]（P <.001）。接受ADL治疗的患者也有类似差异：13例闭合性瘘管患者的血清浓度中位数为7.4μg/ml [6.5 - 10.8]，而6例有引流瘘管患者的血清浓度中位数为4.8μg/ml [1.7 - 6.2]（P =.003）。IFX血清浓度≥5.0μg/ml（曲线下面积为0.92；95%CI：0.82 - 1.00）和ADL血清浓度≥5.9μg/ml（曲线下面积为0.89；95%CI 0.71 - 1.00）与瘘管闭合相关。IFX血清浓度截断值≥5.0μg/ml和ADL血清浓度截断值≥5.9μg/ml与肛周瘘管闭合相关。因此，有引流性肛周瘘管的患者可能受益于强化抗TNF剂量以实现瘘管闭合。
