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炎症性肠病患者血清富含亮氨酸α-2 糖蛋白预处理水平选择抗细胞因子生物制剂。

Selection of anti-cytokine biologics by pretreatment levels of serum leucine-rich alpha-2 glycoprotein in patients with inflammatory bowel disease.

机构信息

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Japan.

出版信息

Sci Rep. 2024 Nov 29;14(1):29755. doi: 10.1038/s41598-024-80285-6.

DOI:10.1038/s41598-024-80285-6
PMID:39613813
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC11607305/
Abstract

Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn's disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02-0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7-13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4-8.3, P < 0.001). The 0w-LRG can predict the effectiveness including serum trough levels of ustekinumab during induction treatment for patients with IBD.

摘要

血清富含亮氨酸α-2 糖蛋白(LRG)可用于监测炎症性肠病(IBD)患者接受生物制剂治疗期间的疾病活动。尚不清楚治疗前血清 LRG 水平是否可以预测 IBD 患者的临床疗效,包括 ustekinumab 的血清谷浓度。这项多中心前瞻性队列研究纳入了 184 名(克罗恩病 104 例,溃疡性结肠炎 80 例)在 2019 年 1 月至 2023 年 3 月期间接受 ustekinumab(n=119)或抗 TNF(n=65)治疗的患者。多变量逻辑回归分析显示,第 0 周(0w)血清 LRG 水平(0w-LRG,优势比 0.12,95%置信区间 0.02-0.68)是第 8 周临床缓解的显著因素之一。我们根据 0w-LRG 的中位数(18.2μg/mL)将患者分为低 LRG 组和高 LRG 组,并比较了两组的疗效。在接受 ustekinumab 治疗的患者中,第 8 周临床缓解的比例在低 LRG 组(76.9%)和高 LRG 组(59.3%,P=0.038)之间有显著差异,第 8 周的血清谷浓度也有显著差异(低 LRG 组为 10.9μg/mL,四分位间距 6.7-13.4;高 LRG 组为 5.3μg/mL,四分位间距 2.4-8.3,P<0.001)。治疗前的 LRG 水平可以预测 IBD 患者诱导治疗期间包括 ustekinumab 血清谷浓度在内的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/7817f06cae97/41598_2024_80285_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/da92535f4942/41598_2024_80285_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/b7aa2837e1dc/41598_2024_80285_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/7817f06cae97/41598_2024_80285_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/da92535f4942/41598_2024_80285_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/b7aa2837e1dc/41598_2024_80285_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04e/11607305/7817f06cae97/41598_2024_80285_Fig3_HTML.jpg

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本文引用的文献

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J Clin Med. 2024 May 17;13(10):2957. doi: 10.3390/jcm13102957.
2
Combination of leucine-rich alpha-2 glycoprotein and fecal markers detect Crohn's disease activity confirmed by balloon-assisted enteroscopy.富含亮氨酸的α-2糖蛋白与粪便标志物联合检测克罗恩病活动度:经气囊辅助小肠镜检查证实
Intest Res. 2024 Jan;22(1):65-74. doi: 10.5217/ir.2023.00092. Epub 2023 Nov 9.
3
The 2023 Impact of Inflammatory Bowel Disease in Canada: Treatment Landscape.
2023年炎症性肠病在加拿大的影响:治疗格局
J Can Assoc Gastroenterol. 2023 Sep 5;6(Suppl 2):S97-S110. doi: 10.1093/jcag/gwad015. eCollection 2023 Sep.
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Real-world effectiveness of vedolizumab compared to anti-TNF agents in biologic-naïve patients with ulcerative colitis: A two-year propensity-score-adjusted analysis from the prospective, observational VEDO -study.生物制剂初治溃疡性结肠炎患者中vedolizumab 与抗 TNF 药物的真实世界疗效比较:前瞻性、观察性 VEDO 研究的两年倾向评分调整分析。
Aliment Pharmacol Ther. 2023 Aug;58(4):429-442. doi: 10.1111/apt.17616. Epub 2023 Jun 15.
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