布罗利尤单抗单药治疗中度至重度特应性皮炎的疗效和安全性：一项系统评价和荟萃分析。

The efficacy and safety of lebrikizumab monotherapy for the management of moderate-to-severe atopic dermatitis: A systematic review and meta-analysis.

作者信息

Bashrahil Bader, Alzahrani Ziyad, Samarkandy Sahal, Aman Abdullah, Jfri Abdulhadi

机构信息

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.

King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.

出版信息

Front Med (Lausanne). 2023 Jan 16;9:1091271. doi: 10.3389/fmed.2022.1091271. eCollection 2022.

BACKGROUND

Atopic dermatitis (AD) is a chronically relapsing disease. Few biologics are approved for moderate-to-severe AD, and novel interventions are emerging. We aimed to evaluate the safety and efficacy of lebrikizumab, an IL-13 immunomodulator, as monotherapy vs. placebo in treating moderate-to-severe AD.

METHODS

Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and ClinicalTrials.gov registry (CT.gov) databases were systematically searched. We evaluated lebrikizumab vs. placebo and measured efficacy using Eczema Area and Severity Index (EASI), Body Surface Area (BSA), and Investigator's Global Assessment (IGA) change from baseline to week 16. Safety was evaluated by the incidence of serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality. The risk of bias was investigated using the Revised Cochrane risk of bias tool.

RESULTS

Three RCTs ( = 1,149) included 543 (47.25%) men vs. 606 (52.75%) women. Meta-analysis showed statistically significant improvement in EASI, IGA, and BSA. EASI75 at week 16 for all regimens was (RR = 2.62, 95% CI [2.06, 3.34], < 0.00001) with the first regimen (500 mg loading dose then 200 mg every 2 weeks) showing the most significant improvement (RR = 3.02, 95% CI [2.39, 3.82], < 0.00001). The pooled analysis of safety outcomes concluded that lebrikizumab did not correlate significantly with the incidence of SAEs, NSAEs, and mortality.

CONCLUSION

Overall, lebrikizumab showed a significant improvement in all efficacy outcomes. Additionally, it did not contribute to any significant incidence of SAEs, NSAEs, or mortality. The risk of bias in included RCTs was minor except in the randomization domain. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of the outcomes ranged from low to high, but predominantly high certainty of evidence.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero/, identifier CRD42022362438.

背景

特应性皮炎（AD）是一种慢性复发性疾病。获批用于中重度AD的生物制剂较少，新的干预措施不断涌现。我们旨在评估白细胞介素-13免疫调节剂lebrikizumab作为单药治疗与安慰剂相比治疗中重度AD的安全性和疗效。

方法

系统检索Cochrane对照试验中心注册库（CENTRAL）、医学期刊数据库（Medline）、荷兰医学文摘数据库（Embase）和临床试验.gov注册库（CT.gov）。我们评估了lebrikizumab与安慰剂，并使用湿疹面积和严重程度指数（EASI）、体表面积（BSA）以及研究者整体评估（IGA）从基线到第16周的变化来衡量疗效。通过严重不良事件（SAE）、非严重不良事件（NSAE）的发生率和死亡率评估安全性。使用修订的Cochrane偏倚风险工具调查偏倚风险。

结果

三项随机对照试验（n = 1149）纳入了543名（47.25%）男性和606名（52.75%）女性。荟萃分析显示，EASI、IGA和BSA有统计学显著改善。所有治疗方案在第16周时达到EASI改善75%的情况为（风险比RR = 2.62，95%置信区间CI [2.06, 3.34]，P < 0.00001），第一种治疗方案（500mg负荷剂量，然后每2周200mg）显示出最显著的改善（RR = 3.02，95% CI [2.39, 3.82]，P < 0.00001）。安全性结果的汇总分析得出结论，lebrikizumab与SAE、NSAE的发生率和死亡率无显著相关性。