在生物暴露程度高的炎症性肠病患者中使用维持性静脉注射优特克单抗优化治疗结果。真实世界中的疗效和调整方案。

Optimizing outcomes with maintenance IV UST in highly bio-exposed patients with IBD. Efficacy and adjusted regimen in real world.

作者信息

Mínguez Alejandro, Coello Elena, Garrido Alejandro, Ripoll Paula, Gomez María, Aguas Mariam, Iborra Marisa, Cerrillo Elena, Tortosa Lluis, Bayarri Virginia, Bueno Noemí, Fernández Maria José, Marqués Remedios, Nos Pilar, Bastida Guillermo

机构信息

IBD Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.

出版信息

Gastroenterol Hepatol. 2025 May;48(5):502253. doi: 10.1016/j.gastrohep.2024.502253. Epub 2024 Sep 11.

DOI:10.1016/j.gastrohep.2024.502253

PMID:39270973

Abstract

BACKGROUND AND AIMS

Ustekinumab is an effective treatment for inflammatory bowel diseases. However, some patients do not respond to conventional doses. The aim of the study was to evaluate the effectiveness of intravenous maintenance ustekinumab in patients with secondary failure.

METHODS

Single-center, retrospective study in adult patients with intravenous maintenance ustekinumab. The reduction of biochemical activity markers, ustekinumab trough levels and clinical indices of activity were evaluated. Biological remission was defined as the percentage decrease fecal calprotectin ≥80% and/or final fecal calprotectin ≤250 and C reactive protein <5mg/L.

RESULTS

Thirty-one patients were included: Crohn's disease 77.4%. All included patients were bio-exposed and 61.3% had carried ≥2 biologics. Pre-intravenous maintenance mean Harvey-Bradshaw Index was 6.5±4.38 vs 5±3.1 at week 8 (p=0.024) vs 4.1±3.1 at week 24 (p=0.019). The median ustekinumab trough level pre-intravenous maintenance was 1.40μg/ml [IQR 2.3] vs 5.35μg/ml [IQR 4.1] at week 8 (p<0.001) vs 4.8μg/ml [IQR 3.9] at week 24 (p<0.001). The pre-intravenous maintenance median fecal calprotectin was 809μg/g [IQR: 2256] vs 423μg/g [IQR: 999] at week 8 (p=0.025) vs 333μg/g [508] (p=0.001) at week 24. At the end of follow-up 48% went into biological remission. The presence of perianal disease was associated with lower biological remission (70.6% vs 27.3%, p=0.025). Median intravenous ustekinumab maintenance time was 8.55 [IQR 23.9] months. In 83.9% of patients no serious infections or malignancy were documented.

CONCLUSIONS

The use of maintenance intravenous ustekinumab appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bio-exposed patients.

摘要

背景与目的

乌司奴单抗是治疗炎症性肠病的一种有效药物。然而，一些患者对常规剂量无反应。本研究的目的是评估静脉注射维持剂量乌司奴单抗对继发治疗失败患者的有效性。

方法

对接受静脉注射维持剂量乌司奴单抗的成年患者进行单中心回顾性研究。评估生化活性标志物的降低情况、乌司奴单抗谷浓度水平及临床活动指标。生物学缓解定义为粪便钙卫蛋白降低百分比≥80%和/或最终粪便钙卫蛋白≤250且C反应蛋白<5mg/L。

结果

纳入31例患者，其中克罗恩病患者占77.4%。所有纳入患者均接受过生物制剂治疗，61.3%的患者使用过≥2种生物制剂。静脉注射维持治疗前的平均哈维-布拉德肖指数为6.5±4.38，第8周时为5±3.1（p=0.024），第24周时为4.1±3.1（p=0.019）。静脉注射维持治疗前乌司奴单抗谷浓度中位数为1.40μg/ml[四分位间距2.3]，第8周时为5.35μg/ml[四分位间距4.1]（p<0.001），第24周时为4.8μg/ml[四分位间距3.9]（p<0.001）。静脉注射维持治疗前粪便钙卫蛋白中位数为809μg/g[四分位间距：2256]，第8周时为423μg/g[四分位间距：999]（p=0.025），第24周时为333μg/g[508]（p=0.001）。随访结束时，48%的患者实现生物学缓解。肛周疾病的存在与较低的生物学缓解率相关（70.6%对27.3%，p=0.025）。静脉注射乌司奴单抗的维持治疗时间中位数为8.55[四分位间距23.9]个月。83.9%的患者未记录到严重感染或恶性肿瘤。