Wang Huan, Zheng Jiaqi, Zhang Qing, Tian Zhongping, Sun Yuhang, Zhu Tianyi, Bi Yanlong, Zhang Li
Clinical Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
Front Pharmacol. 2024 Nov 12;15:1410172. doi: 10.3389/fphar.2024.1410172. eCollection 2024.
Clinical trials in recent years have shown significant effectiveness of complement inhibitors for geographic atrophy (GA) treatment. Two complement inhibitor drugs have been approved by the Food and Drug Administration (FDA).
to compare and rank the different complement inhibitors in the treatment of GA secondary to age-related macular degeneration (AMD).
A systematic literature search was conducted in the Cochrane Central, Web of Science Core Collection, PubMed, LWW Medical Journals, ClinicalTrials.gov, and WHO ICTRP from inception to October 2023.
All randomized clinical trials evaluating the effectiveness of complement inhibitors in patients diagnosed with secondary GA in AMD were identified.
This study followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) network meta-analysis Checklist of Items and the Cochrane Risk of Bias Assessment Tool for assessing the study quality. Multiple authors independently coded all titles and abstracts, reviewed full-text articles against the inclusion and exclusion criteria, and resolved all discrepancies by consensus. Random-effects network meta-analyses were applied. Bayesian network meta-analysis was performed using the BUGSnet package in R (4.2.0).
The primary efficacy outcome was the change in GA lesion size (mm) from baseline to month 12. The secondary efficacy outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to month 12. Safety outcome measures included the number of subjects with serious adverse events (SAEs) and macular neovascularization (MNV).
Ten randomized controlled trials including 4,405 participants and five complement inhibitors were identified. Comparison with sham and SUCRA analysis showed that avacincaptad pegol 2 mg (MD: -0.58, 95% CrI: -0.97 to -0.18, SUCRA: 93.55), pegcetacoplan monthly (MD: -0.38, 95% CrI: -0.57 to -0.20, SUCRA: 81.37), and pegcetacoplan every other month (MD: -0.30, 95% CrI: -0.49 to -0.11, SUCRA: 70.16) have significant changes in GA lesion reduction. No treatments showed significant changes in BCVA and SAE compared with sham. Pegcetacoplan monthly (OR: 4.30, 95% CrI: 1.48-16.72) increased the risk of MNV. Avacincaptad pegol 2 mg demonstrated favorable outcomes in terms of SAE and MNV.
Avacincaptad pegol 2 mg is the most effective complement inhibitor with better safety for the treatment of GA secondary to AMD.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351515, Identifier PROSPERO CRD42022351515.
近年来的临床试验表明补体抑制剂在治疗地图样萎缩（GA）方面具有显著疗效。两种补体抑制剂药物已获得美国食品药品监督管理局（FDA）批准。
比较并对不同补体抑制剂在治疗年龄相关性黄斑变性（AMD）继发GA中的效果进行排名。
从创刊至2023年10月，在考克兰中央对照试验注册库、科学网核心合集、PubMed、LWW医学期刊、ClinicalTrials.gov和世界卫生组织国际临床试验注册平台进行了系统文献检索。
确定了所有评估补体抑制剂对诊断为AMD继发GA患者有效性的随机临床试验。
本研究遵循系统评价和Meta分析的首选报告项目（PRISMA）网络Meta分析项目清单以及考克兰偏倚风险评估工具来评估研究质量。多位作者独立对所有标题和摘要进行编码，根据纳入和排除标准审查全文，并通过共识解决所有分歧。应用随机效应网络Meta分析。使用R（4.2.0）中的BUGSnet软件包进行贝叶斯网络Meta分析。
主要疗效结局是从基线到第12个月GA病变大小（mm）的变化。次要疗效结局是从基线到第12个月最佳矫正视力（BCVA）的平均变化。安全性结局指标包括发生严重不良事件（SAE）和黄斑新生血管（MNV）的受试者数量。
确定了10项随机对照试验，包括4405名参与者和5种补体抑制剂。与假治疗组比较及累积排序曲线下面积（SUCRA）分析显示，阿伐西普他德聚乙二醇2mg（MD：-0.58，95%可信区间（CrI）：-0.97至-0.18，SUCRA：93.55）、每月一次培西加可普朗（MD：-0.38，95%CrI：-0.57至-0.20，SUCRA：81.37）和每两个月一次培西加可普朗（MD：-0.30，95%CrI：-0.49至-0.11，SUCRA：70.16）在GA病变缩小方面有显著变化。与假治疗组相比，没有治疗在BCVA和SAE方面显示出显著变化。每月一次培西加可普朗（比值比（OR）：4.30，95%CrI：1.48 - 16.72）增加了MNV的风险。阿伐西普他德聚乙二醇2mg在SAE和MNV方面显示出良好结局。
阿伐西普他德聚乙二醇2mg是治疗AMD继发GA最有效的补体抑制剂，安全性更好。
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351515，标识符PROSPERO CRD42022351515。
