不同药物和剂量的抗血管内皮生长因子(aflibercept、bevacizumab、conbercept、ranibizumab)与激光治疗早产儿视网膜病变的比较:网络荟萃分析。

IF 5.1 2区 医学 Q1 OPHTHALMOLOGY
Amparo Ortiz-Seller , Pablo Martorell , Honorio Barranco , Isabel Pascual-Camps , Esteban Morcillo , José L. Ortiz
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引用次数: 0

摘要

激光光凝(LPC)和/或玻璃体内注射抗血管内皮生长因子(anti-VEGF)是目前治疗早产儿视网膜病变(ROP)的标准方法。由于最佳抗血管内皮生长因子剂量仍存在争议,因此本网络荟萃分析的重点是,以再治疗率为主要结果,以再治疗时间和屈光不正为次要终点,是否可以确定不同剂量水平的玻璃体内注射抗血管内皮生长因子药物(阿弗利百普、贝伐珠单抗、康柏西普、雷尼珠单抗)作为 ROP 的主要治疗方法与激光相比的干预排名。从数据库(2005 年 1 月至 2023 年 6 月)中检索了 68 项研究(15 项随机对照试验和 53 项非随机研究),涉及 6445 名婴儿的 12356 只眼睛。在网络元分析(CINeMA)中对各项研究的模型拟合度、偏倚风险和证据置信度进行了评估。贝叶斯 NMA 显示,就再治疗率而言,抗血管内皮生长因子药物并不逊色于激光。就玻璃体内贝伐单抗(IVB)而言,常规婴儿剂量一半的剂量显示再治疗率风险较低(风险比(RR)为 1.43;95% 可信区间(CrI):0.508, 4.03)。从累积排序曲线(SUCRA)图的概率排序来看,半量贝伐珠单抗的位置优于常规剂量和增量剂量(常规剂量的1.2-2倍)。阿弗利贝赛和雷尼珠单抗的半剂量与常规剂量也有类似的概率趋势。康柏西普常规婴儿剂量的再治疗风险最低(RR 0.846;95% CrI:0.245,2.91)。在次要终点方面,较低剂量的抗血管内皮生长因子药物与较短的再治疗时间相关。贝伐珠单抗和雷尼珠单抗(0.3 毫克)的增大剂量变化最大,平均值分别为 14.1 周(95% CrI:6.65,21.6)和 12.8 周(95% CrI:3.19,20.9)。最后,NMA 显示抗 VEGF 的屈光曲线优于激光疗法,尤其是贝伐珠单抗和雷尼单抗的常规婴儿剂量,其屈光曲线明显优于 LPC,平均差异分别为 1.67(球面等效-屈光度)(95% CrI:0.705,2.67)和 2.19(95% CrI:0.782,3.59)。在 SUCRA 图中,LPC 的位置明显不同,近视概率更高。还需要进一步的临床试验来比较不同剂量的抗血管内皮生长因子药物,但我们的研究结果表明,低剂量的这些药物仍能保持疗效,并可减少眼部和全身的不良反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. – 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2–2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.

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来源期刊
Survey of ophthalmology
Survey of ophthalmology 医学-眼科学
CiteScore
10.30
自引率
2.00%
发文量
138
审稿时长
14.8 weeks
期刊介绍: Survey of Ophthalmology is a clinically oriented review journal designed to keep ophthalmologists up to date. Comprehensive major review articles, written by experts and stringently refereed, integrate the literature on subjects selected for their clinical importance. Survey also includes feature articles, section reviews, book reviews, and abstracts.
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