De Gregorio Michael, Lee Tanya, Krishnaprasad Krupa, Amos Gregory, An Yoon-Kyo, Bastian-Jordan Matthew, Begun Jakob, Borok Nira, Brown Dougal J M, Cheung Wa, Connor Susan J, Gerstenmaier Jan, Gilbert Lauren E, Gilmore Robert, Gu Bonita, Kutaiba Numan, Lee Allan, Mahy Gillian, Srinivasan Ashish, Thin Lena, Thompson Alexander J, Welman Christopher J, Yong Eric X Z, De Cruz Peter, van Langenberg Daniel, Sparrow Miles P, Ding Nik S
St Vincent's Hospital Melbourne, Department of Gastroenterology, Fitzroy, Australia; University of Melbourne, Medicine, Parkville, Australia.
St Vincent's Hospital Melbourne, Department of Gastroenterology, Fitzroy, Australia.
Clin Gastroenterol Hepatol. 2022 Jun;20(6):1306-1314. doi: 10.1016/j.cgh.2021.07.053. Epub 2021 Aug 11.
BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease.
A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0).
Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 μg/mL; adalimumab 9.1 vs 6.2 μg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 μg/mL; P < .05; adalimumab 9.8 vs 6.2 μg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles.
Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.
抗肿瘤坏死因子-α（TNF）药物水平升高与克罗恩病肛周瘘管的临床愈合改善相关。目前尚不清楚这是否会导致放射学评估中的愈合改善。我们旨在评估抗TNF药物水平与肛周瘘管型克罗恩病放射学结局之间的关联。
进行了一项横断面回顾性多中心研究。纳入接受英夫利昔单抗或阿达木单抗维持治疗且在肛周磁共振成像6个月内有药物水平记录的肛周瘘管型克罗恩病患者。排除在药物水平检测和成像之间接受剂量调整或瘘管手术的患者。使用范阿舍指数对放射学疾病活动进行评分，并使用以下指标计算炎症子评分：T2加权成像高信号、直径>3mm的积液、直肠壁受累情况。主要终点是放射学愈合（炎症子评分≤6）。次要终点是放射学缓解（炎症子评分 = 0）。
193例患者（英夫利昔单抗组117例，阿达木单抗组76例）中，放射学愈合患者的药物中位水平高于疾病活动患者（英夫利昔单抗分别为6.0 vs 3.9μg/mL；阿达木单抗分别为9.1 vs 6.2μg/mL；P均<0.05）。放射学缓解患者的药物中位水平也高于疾病活动患者（英夫利昔单抗分别为7.4 vs 3.9μg/mL；P<0.05；阿达木单抗分别为9.8 vs 6.2μg/mL；P = 0.07）。随着抗TNF药物水平三分位数升高，炎症子评分中位数显著逐步降低。
在肛周瘘管型克罗恩病中，较高的抗TNF药物水平与磁共振成像的放射学结局改善相关，英夫利昔单抗和阿达木单抗在较高药物水平三分位数时均有逐步改善。
