瑞莎珠单抗与克罗恩病患者生物标志物的正常化相关：3期ADVANCE、MOTIVATE和FORTIFY研究结果

Risankizumab Is Associated With Normalization of Biomarkers in Patients With Crohn's Disease: Results From the Phase 3 ADVANCE, MOTIVATE, and FORTIFY Studies.

作者信息

Atreya Raja, Ferrante Marc, Panaccione Remo, Feagan Brian, Shchukina Oksana, Jairath Vipul, Rieder Florian, Hisamatsu Tadakazu, Siegmund Britta, Kligys Kristina, Song Alexandra, Zambrano Javier, Mallick Madhuja, Zhang Yafei, Armuzzi Alessandro, D'Haens Geert

机构信息

Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

出版信息

J Crohns Colitis. 2025 Apr 4;19(4). doi: 10.1093/ecco-jcc/jjae164.

DOI:10.1093/ecco-jcc/jjae164

PMID:39485390

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12001336/

Abstract

BACKGROUND AND AIMS

Normalization of high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) are suggested as intermediate treatment targets for Crohn's disease (CD). This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab.

METHODS

This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP (>5 mg/L) or FCP (>250 µg/g) concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study. We assessed the proportion of patients achieving biomarker normalization, defined as hs-CRP ≤5 mg/L and FCP ≤250 µg/g, and the association between achieving biomarker normalization and improved clinical and endoscopic outcomes.

RESULTS

Among 748 patients with elevated baseline hs-CRP or FCP concentrations, higher proportions of patients treated with risankizumab vs placebo achieved normalization of hs-CRP (Week 12: placebo, 17.5%; risankizumab 600 mg, 48.5%; Week 52: placebo, 29.5%; risankizumab 180 mg, 45.2%; risankizumab 360 mg, 40.8%) and FCP (Week 12: placebo, 9.1%; risankizumab 600 mg, 26.0%; Week 52: placebo, 28.0%; risankizumab 180 mg, 43.0%; risankizumab 360 mg, 44.0%; nominal p < 0.05 vs placebo for all comparisons). Achievement of both clinical or endoscopic outcomes and improvement of biomarker concentrations occurred at higher rates among patients treated with risankizumab vs placebo, regardless of prior exposure to biologic therapies.

CONCLUSIONS

Risankizumab treatment led to sustained normalization of inflammatory biomarkers with improved clinical and endoscopic results.

CLINICAL TRIAL REGISTRATION NUMBER

ADVANCE, NCT03105128; MOTIVATE, NCT03104413; FORTIFY, NCT03105102.

摘要

背景与目的

高敏C反应蛋白（hs-CRP）和粪便钙卫蛋白（FCP）的正常化被认为是克罗恩病（CD）的中间治疗目标。本分析评估了接受瑞莎珠单抗治疗的患者生物标志物正常化的实现情况，以及生物标志物浓度改善与临床和内镜检查结果之间的关系。

方法

这项事后分析纳入了来自12周的ADVANCE和MOTIVATE诱导研究以及52周的FORTIFY维持研究中，基线hs-CRP浓度升高（>5mg/L）或FCP浓度升高（>250μg/g）的中度至重度活动性CD患者。我们评估了实现生物标志物正常化（定义为hs-CRP≤5mg/L且FCP≤250μg/g）的患者比例，以及实现生物标志物正常化与改善临床和内镜检查结果之间的关联。

结果

在748例基线hs-CRP或FCP浓度升高的患者中，与安慰剂相比，接受瑞莎珠单抗治疗的患者hs-CRP正常化的比例更高（第12周：安慰剂组为17.5%；瑞莎珠单抗600mg组为48.5%；第52周：安慰剂组为29.5%；瑞莎珠单抗180mg组为45.2%；瑞莎珠单抗360mg组为40.8%），FCP正常化的比例也更高（第12周：安慰剂组为9.1%；瑞莎珠单抗600mg组为26.0%；第52周：安慰剂组为28.0%；瑞莎珠单抗180mg组为43.0%；瑞莎珠单抗360mg组为44.0%；所有比较中与安慰剂相比的名义p<0.05）。无论先前是否接受过生物治疗，与安慰剂相比，接受瑞莎珠单抗治疗的患者实现临床或内镜检查结果以及生物标志物浓度改善的比例更高。