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皮下注射与静脉注射白细胞介素12/23抑制剂治疗中重度克罗恩病缓解的疗效比较:一项系统综述和荟萃分析

Comparative Efficacy of Subcutaneous Versus Intravenous Interleukin 12/23 Inhibitors for the Remission of Moderate to Severe Crohn's Disease: A Systematic Review and Meta-Analysis.

作者信息

Alwisi Nouran, Ismail Rana, Al-Kuwari Hissa, Al-Ansari Khalifa H, Al-Matwi Mohammed A, Aweer Noor A, Al-Marri Wejdan N, Al-Kubaisi Yousif, Al-Mohannadi Muneera, Hamran Shahd, Doi Suhail A R, Farooqui Habib H, Chivese Tawanda

机构信息

College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.

Department of Gastroenterology and Hepatology, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar.

出版信息

Biomedicines. 2025 Mar 12;13(3):702. doi: 10.3390/biomedicines13030702.

Abstract

: Interleukin 12/23 inhibitors are a newer class of monoclonal antibodies used to induce and maintain remission for Crohn's disease (CD), a chronic inflammatory bowel disease, when patients do not respond to conventional immunomodulatory drugs or first-line monoclonal antibody therapies. Although biologics are best administered intravenously, subcutaneous administration has been trialed, with mixed results. This research synthesized evidence on the efficacy and safety of subcutaneous compared to intravenous administration of interleukin 12/23 inhibitors for moderate to severe CD. : In this systematic review and meta-analysis, we searched Cochrane, PubMed, SCOPUS, CINHAL, and preprint archives for randomized controlled trials (RCTs) that compared the efficacy and safety of subcutaneous to intravenous interleukin 12/23 inhibitors for the remission of CD. After study quality assessment, a meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model, heterogeneity was assessed using I, and publication bias was performed using Doi plots. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). : Seven RCTs, with 2179 participants, all with moderate to severe CD, were included. After meta-analysis, subcutaneous compared to intravenous administration showed similar efficacy for the induction of remission (OR 0.77, 95%CI 0.53-1.12), with no-to-low heterogeneity (I = 0%, = 0.97). For the maintenance of remission, only two studies had analyzable data, and they showed that subcutaneous interleukin 12/23 inhibitors were equal or better compared to intravenous administration. Further syntheses showed that subcutaneous compared to intravenous administration of interleukin 12/23 inhibitors had almost similar odds of adverse events (OR 0.91, 95%CI 0.63-1.32, I = 39%), serious adverse events (OR 0.97, 95%CI 0.61-1.53, I = 0%), and treatment discontinuation (OR 1.06, 95%CI 0.67-1.68, I = 0%). : In individuals with moderate to severe CD, subcutaneous administration has similar efficacy for inducing remission with comparable safety. More RCTs are needed to confirm these findings.

摘要

白细胞介素12/23抑制剂是一类新型单克隆抗体,用于诱导和维持克罗恩病(CD,一种慢性炎症性肠病)的缓解,适用于对传统免疫调节药物或一线单克隆抗体疗法无反应的患者。尽管生物制剂最好通过静脉给药,但皮下给药也已进行试验,结果不一。本研究综合了皮下注射与静脉注射白细胞介素12/23抑制剂治疗中度至重度CD的疗效和安全性证据。

在这项系统评价和荟萃分析中,我们在Cochrane、PubMed、SCOPUS、CINHAL和预印本档案中检索了随机对照试验(RCT),这些试验比较了皮下注射与静脉注射白细胞介素12/23抑制剂治疗CD缓解的疗效和安全性。在研究质量评估后,使用偏倚调整后的逆方差异质性模型进行荟萃分析,使用I²评估异质性,并使用Doi图进行发表偏倚分析。使用推荐分级、评估、制定和评价(GRADE)评估证据确定性。

纳入了7项RCT,共2179名参与者,均为中度至重度CD患者。荟萃分析后,皮下注射与静脉注射相比,诱导缓解的疗效相似(OR=0.77,95%CI 0.53-1.12),异质性为无至低(I²=0%,P=0.97)。对于维持缓解,只有两项研究有可分析的数据,结果显示皮下注射白细胞介素12/23抑制剂与静脉注射相比效果相同或更好。进一步的综合分析表明,皮下注射与静脉注射白细胞介素12/23抑制剂相比,不良事件(OR=0.91,95%CI 0.63-1.32,I²=39%)、严重不良事件(OR=0.97,95%CI 0.61-1.53,I²=0%)和治疗中断(OR=1.06,95%CI 0.67-1.68,I²=0%)的几率几乎相似。

对于中度至重度CD患者,皮下给药在诱导缓解方面疗效相似,安全性相当。需要更多的RCT来证实这些发现。

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