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Abstract：
Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn\'s disease (CD).
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.
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.
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, I2 = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I2 = 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).
Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD.
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.
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.
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, I2 = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I2 = 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).
Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD.
摘要：
背景：靶向白细胞介素-23（IL-23）是克罗恩病（CD）的重要治疗策略。
目的：本系统综述和荟萃分析评估了选择性IL-23p19和IL-12/23p40抑制剂在中度至重度CD患者中的疗效和安全性。
方法：MEDLINE，Embase,从成立到2023年5月24日，对Cochrane文库(CENTRAL)进行了随机检索，儿童和成人CD患者选择性IL-23p19和IL-12/23p40抑制剂的安慰剂对照或活性对照诱导和/或维持试验。主要结果是临床缓解患者的比例。次要结果是临床反应，内镜缓解,内镜反应,和安全。使用随机效应模型汇集数据。使用Cochrane偏倚风险工具和GRADE标准评估偏倚风险和证据确定性。分别。
结果：纳入18项试验（n=5561）。大多数研究被评为低偏倚风险。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=3.20,95CI2.17-4.70)缓解和维持临床缓解(RR=1.39,95CI1.10-1.77)方面显著优于安慰剂(所有结果的GRADE高确定性证据)。亚组分析显示，靶向IL-23优于安慰剂，用于诱导生物学初治的临床缓解（RR=2.20，95CI1.46-3.32，I2=0％，p=0.39）和有生物学经验的患者（RR=1.82，95CI1.27-2.60，I2=56.5％，p=0.01)。与安慰剂相比，靶向IL-23与诱导（RR=0.55，95CI0.44-0.73）和维持（RR=0.72，95CI0.53-0.98）试验中严重不良事件的风险降低相关（高确定性证据）。
结论：靶向IL-23对于诱导和维持中度至重度CD患者的临床和内镜缓解是有效和安全的。
目的：本系统综述和荟萃分析评估了选择性IL-23p19和IL-12/23p40抑制剂在中度至重度CD患者中的疗效和安全性。
方法：MEDLINE，Embase,从成立到2023年5月24日，对Cochrane文库(CENTRAL)进行了随机检索，儿童和成人CD患者选择性IL-23p19和IL-12/23p40抑制剂的安慰剂对照或活性对照诱导和/或维持试验。主要结果是临床缓解患者的比例。次要结果是临床反应，内镜缓解,内镜反应,和安全。使用随机效应模型汇集数据。使用Cochrane偏倚风险工具和GRADE标准评估偏倚风险和证据确定性。分别。
结果：纳入18项试验（n=5561）。大多数研究被评为低偏倚风险。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=3.20,95CI2.17-4.70)缓解和维持临床缓解(RR=1.39,95CI1.10-1.77)方面显著优于安慰剂(所有结果的GRADE高确定性证据)。亚组分析显示，靶向IL-23优于安慰剂，用于诱导生物学初治的临床缓解（RR=2.20，95CI1.46-3.32，I2=0％，p=0.39）和有生物学经验的患者（RR=1.82，95CI1.27-2.60，I2=56.5％，p=0.01)。与安慰剂相比，靶向IL-23与诱导（RR=0.55，95CI0.44-0.73）和维持（RR=0.72，95CI0.53-0.98）试验中严重不良事件的风险降低相关（高确定性证据）。
结论：靶向IL-23对于诱导和维持中度至重度CD患者的临床和内镜缓解是有效和安全的。
