白细胞介素-12/23 和白细胞介素-23 抑制剂治疗溃疡性结肠炎的有效性和安全性:随机对照试验的系统综述和元分析》。

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY American journal of therapeutics Pub Date : 2024-08-30 DOI:10.1097/MJT.0000000000001766
Fouad Jaber, Mohammed Ayyad, Saqr Alsakarneh, Tala Alsharaeh, Ahmed-Jordan Salahat, Mohammad Jaber, Manesh Kumar Gangwani, Yazan Abboud, Islam Mohamed, Hassam Ali, Yassine Kilani, Francis A Farraye, Jana G Hashash
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引用次数: 0

摘要

研究背景靶向白细胞介素-23(IL-23)是治疗溃疡性结肠炎(UC)的重要途径:研究问题:针对IL-23p19和IL-12/23p40的选择性抑制剂对中重度UC患者的有效性和安全性如何?研究设计:截至 2024 年 1 月 15 日,对 MEDLINE、Embase、Scopus 和 Cochrane 数据库进行了系统检索,以确定在 UC 患者中比较 IL-23p19 和 IL-12/23p40 抑制剂与安慰剂或活性比较药的随机对照试验。主要结果是临床缓解,次要结果包括临床反应、内镜缓解以及诱导和维持阶段的安全性。采用固定效应模型,我们将二分法数据与风险比(RR)和95%置信区间(CI)进行了汇总分析:在涉及1120名中重度UC患者的5项试验中,靶向IL-23在诱导临床缓解[RR:2.08,95% CI,(1.66-2.61)]、内镜缓解[RR:1.73,95% CI,(1.39-2.16)]和组织学缓解[RR:1.88,95% CI,(1.34-2.64)]方面显示出明显的优越性。此外,接受IL-12/23p40或IL-23p19拮抗剂治疗的患者可维持临床缓解[RR:1.85,95% CI,(1.53-2.23)]、内镜缓解[RR:2.03,95% CI,(1.60-2.57)]和组织学缓解[RR:1.66,95% CI,(1.11-2.48)]。与在诱导期接受安慰剂的患者相比,靶向IL-23可降低诱导期[RR:0.94,95% CI,(0.86-1.02)]和维持期[RR:0.93,95% CI,(0.86-0.99)]任何不良事件(AE)、诱导期任何严重AE[RR:0.53,95% CI,(0.36-0.78)]以及因AE而停药的风险[RR:0.24,95% CI (0.14,0.43)]:结论:IL-23靶向药物对诱导和维持中重度UC患者的临床和内镜缓解具有有效性和安全性。
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Efficacy and Safety of Interleukin-12/23 and Interleukin-23 Inhibitors for Ulcerative Colitis: A Systematic Review Ad Meta-Analysis of Randomized Controlled Trials.

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC).

Study question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC?

Data sources: MEDLINE, Embase, Scopus, and Cochrane databases.

Study design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis.

Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)].

Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

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来源期刊
American journal of therapeutics
American journal of therapeutics PHARMACOLOGY & PHARMACY-
CiteScore
5.50
自引率
9.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: American Journal of Therapeutics is an indispensable resource for all prescribing physicians who want to access pharmacological developments in cardiology, infectious disease, oncology, anesthesiology, nephrology, toxicology, and psychotropics without having to sift through stacks of medical journals. The journal features original articles on the latest therapeutic approaches as well as critical articles on the drug approval process and therapeutic reviews covering pharmacokinetics, regulatory affairs, pediatric clinical pharmacology, hypertension, metabolism, and drug delivery systems.
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