Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System.
Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e401-e406. doi: 10.1097/MEG.0000000000002116.
We investigated relationships between induction ustekinumab levels and clinical and biochemical outcomes in Crohn's disease.
Following standard IV induction, ustekinumab levels were measured at week 2 (wk2) and week 6 (wk6). Ustekinumab levels were compared in patients receiving 260, 390 and 520 mg at induction. Crohn's disease activity index (CDAI), serum albumin, C-reactive protein (CRP) and fecal calprotectin (FCP) were measured at baseline and week 12 (wk12). Associations between ustekinumab levels and these parameters were assessed. Ustekinumab levels were compared between patients requiring dose intensification within one year of induction and those remaining on standard dosing.
Of 23 wk2 ustekinumab levels, 22(95.7%) were above the upper limit of quantification of the assay (25 µg/mL). Median wk6 ustekinumab level (n = 25) was 14.2 μg/mL [interquartile range (IQR), 9.6-20.1]. Median wk6 ustekinumab levels in patients receiving 260, 390 and 520 mg were 8.6, 16.3 and 25.0 µg/mL, respectively, P = 0.01. There were significant correlations between baseline albumin and wk6 ustekinumab levels; r = 0.644 [95% confidence interval (CI), 0.304-0.839], P < 0.001, and between baseline FCP and wk6 ustekinumab levels; r = -0.678 (95% CI, -0.873 to -0.296), P < 00.01. Median wk12 CDAI (n = 18), CRP (n = 22) and FCP (n = 13) were 78 (IQR, 52.5-152), 1.75 mg/L (IQR, 0.93-7.03) and 746 μg/g (IQR, 259-2100), respectively. There were significant correlations between wk6 ustekinumab levels and wk12 CDAI; r = -0.513 (95% CI, -0.796 to -0.046), P = 0.03; and between wk6 ustekinumab levels and wk12 CRP; r = -0.578 (95% CI, -0.808 to -0.194), P < 0.01. Wk6 ustekinumab levels were lower in patients undergoing subsequent dose intensification; 12.5 vs. 19.6 µg/mL, P = 0.04.
Wk6 ustekinumab levels are significantly associated with baseline Crohn's disease biomarkers and subsequent clinical and biochemical outcomes.
我们研究了克罗恩病诱导乌司奴单抗水平与临床和生化结局之间的关系。
在标准 IV 诱导后，分别在第 2 周（wk2）和第 6 周（wk6）检测乌司奴单抗水平。比较接受 260、390 和 520 mg 诱导剂量的患者的乌司奴单抗水平。在基线和第 12 周（wk12）测量克罗恩病活动指数（CDAI）、血清白蛋白、C 反应蛋白（CRP）和粪便钙卫蛋白（FCP）。评估乌司奴单抗水平与这些参数之间的关系。比较一年内需要剂量强化的患者与标准剂量组患者的乌司奴单抗水平。
在 23 份 wk2 乌司奴单抗水平中，22 份（95.7%）高于检测方法的定量上限（25 µg/mL）。25 名患者的中位 wk6 乌司奴单抗水平（n = 25）为 14.2 µg/mL[四分位距（IQR），9.6-20.1]。接受 260、390 和 520 mg 的患者的中位 wk6 乌司奴单抗水平分别为 8.6、16.3 和 25.0 µg/mL，P = 0.01。基线白蛋白与 wk6 乌司奴单抗水平之间存在显著相关性；r = 0.644[95%置信区间（CI），0.304-0.839]，P < 0.001，基线 FCP 与 wk6 乌司奴单抗水平之间存在显著相关性；r = -0.678（95%CI，-0.873 至 -0.296），P < 0.01。18 名患者的中位 wk12 CDAI（n = 18）、CRP（n = 22）和 FCP（n = 13）分别为 78（IQR，52.5-152）、1.75 mg/L（IQR，0.93-7.03）和 746 μg/g（IQR，259-2100）。wk6 乌司奴单抗水平与 wk12 CDAI 之间存在显著相关性；r = -0.513（95%CI，-0.796 至 -0.046），P = 0.03；与 wk6 乌司奴单抗水平与 wk12 CRP 之间存在显著相关性；r = -0.578（95%CI，-0.808 至 -0.194），P < 0.01。随后进行剂量强化的患者的 wk6 乌司奴单抗水平较低；12.5 对 19.6 µg/mL，P = 0.04。
wk6 乌司奴单抗水平与克罗恩病的基线生物标志物和随后的临床及生化结局显著相关。
