IL-12/23 和 IL-23 抑制剂治疗克罗恩病的疗效和安全性：系统评价和荟萃分析。
Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis.
机构信息
Division of Gastroenterology, Department of Medicine, Western University, 1151 Richmond St, London, ON, N6A 5C1, Canada.
Alimentiv Inc., 100 Dundas St Suite 200, London, ON, N6A 5B6, Canada.
出版信息
Dig Dis Sci. 2023 Sep;68(9):3702-3713. doi: 10.1007/s10620-023-08014-z. Epub 2023 Jun 28.
BACKGROUND
Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD).
AIMS
This systematic review and meta-analysis assessed the efficacy and safety of selective IL-23p19 and IL-12/23p40 inhibitors in patients with moderate-to-severe CD.
METHODS
MEDLINE, Embase, and the Cochrane library (CENTRAL) were searched from inception to May 24, 2023, for randomized, placebo- or active comparator-controlled induction and/or maintenance trials of selective IL-23p19 and IL-12/23p40 inhibitors in pediatric and adult patients with CD. The primary outcome was the proportion of patients in clinical remission. Secondary outcomes were clinical response, endoscopic remission, endoscopic response, and safety. Data were pooled using a random-effects model. Risk of bias and certainty of evidence were assessed using the Cochrane risk of bias tool and the GRADE criteria, respectively.
RESULTS
Eighteen trials (n = 5561) were included. Most studies were rated as low risk of bias. Targeting IL-23 was significantly superior to placebo for inducing clinical (risk ratio [RR] = 1.87, 95% confidence interval [CI] 1.58-2.21) and endoscopic (RR = 3.20, 95%CI 2.17-4.70) remission and maintaining clinical remission (RR = 1.39, 95%CI 1.10-1.77) (GRADE high certainty evidence for all outcomes). Subgroup analysis showed that targeting IL-23 was superior to placebo for inducing clinical remission in biologic-naïve (RR = 2.20, 95%CI 1.46-3.32, I = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I = 56.5%, p = 0.01). Targeting IL-23 was associated with a decreased risk of serious adverse events in induction (RR = 0.55, 95%CI 0.44-0.73) and maintenance (RR = 0.72, 95%CI 0.53-0.98) trials compared to placebo (high certainty evidence).
CONCLUSION
Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD.
背景
靶向白细胞介素-23（IL-23）是治疗克罗恩病（CD）的重要治疗策略。
目的
本系统评价和荟萃分析评估了选择性 IL-23p19 和 IL-12/23p40 抑制剂在中重度 CD 患者中的疗效和安全性。
方法
从建库到 2023 年 5 月 24 日，检索 MEDLINE、Embase 和 Cochrane 图书馆（CENTRAL），以评估儿科和成人 CD 患者中选择性 IL-23p19 和 IL-12/23p40 抑制剂的诱导和/或维持试验的随机、安慰剂或活性对照试验。主要结局是临床缓解患者的比例。次要结局是临床应答、内镜缓解、内镜应答和安全性。使用随机效应模型汇总数据。使用 Cochrane 偏倚风险工具和 GRADE 标准分别评估风险偏倚和证据确定性。
结果
纳入了 18 项试验（n=5561）。大多数研究的偏倚风险较低。与安慰剂相比，靶向 IL-23 在诱导临床（风险比 [RR] = 1.87，95%置信区间 [CI] 1.58-2.21）和内镜（RR = 3.20，95%CI 2.17-4.70）缓解和维持临床缓解（RR = 1.39，95%CI 1.10-1.77）方面具有显著优势（所有结局均为 GRADE 高确定性证据）。亚组分析表明，与安慰剂相比，在生物初治（RR = 2.20，95%CI 1.46-3.32，I=0%，p=0.39）和生物经验丰富的患者（RR = 1.82，95%CI 1.27-2.60，I=56.5%，p=0.01）中，靶向 IL-23 更能诱导临床缓解。与安慰剂相比，靶向 IL-23 可降低诱导（RR = 0.55，95%CI 0.44-0.73）和维持（RR = 0.72，95%CI 0.53-0.98）试验中严重不良事件的风险（高确定性证据）。
结论
靶向 IL-23 可有效诱导和维持中重度 CD 患者的临床和内镜缓解，且安全性良好。
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