Topic

To compare bevacizumab, ranibizumab, aflibercept, and laser treatment as primary therapies for retinopathy of prematurity (ROP) in terms of retreatment rate.

Clinical relevance

Anti-VEGF agents are increasingly used as primary treatment for ROP and may provide superior outcomes compared with laser in posterior disease. Head-to-head comparisons between different anti-VEGFs are lacking.

Methods

We searched CENTRAL, Embase, MEDLINE, and CINAHL databases for randomized controlled trials and nonrandomized comparative studies that had been reported as of March 2022. We included studies that used bevacizumab, ranibizumab, aflibercept or laser for ROP with comparable cohorts and treatment criteria. Studies were evaluated by the Grading of Recommendations, Assessment, Development and Evaluation framework, and those with biased case selection, nonrandomized case-control, or lack of control group were excluded. Frequentist meta-analyses of proportions determined the absolute primary retreatment rate of each modality and Bayesian network meta-analyses compared pairs of treatments in type 1 and Zone I ROP.

Results

In all, 30 studies (4686 eyes) were included in the network meta-analyses. For type 1 ROP, single-treatment success rates (i.e., likelihood of needing no further treatment) were 89.3% (95% confidence interval [CI]: 83.8%–93.8%; n = 1552) for laser, 87.0% (95% CI: 78.6%–93.8%; n = 2081) for bevacizumab, 80.7% (95% CI: 62.0%–94.4%; n = 326) for aflibercept, and 74.0% (95% CI: 62.7%–84.1%; n = 727) for ranibizumab. Bayesian network meta-analysis indicates that laser treatment is associated with a significant 62% (95% credible interval [CrI]: 16%–83%) reduction in retreatment risk compared with ranibizumab, while no significant difference was found among other pairwise comparisons. The mean ± standard error of the mean times to secondary treatment following primary aflibercept (12.96 ± 0.47 weeks) and bevacizumab (11.36 ± 0.54 weeks) therapy were significantly longer than that for primary ranibizumab (9.29 ± 0.43weeks) therapy (P = 7 × 10⁻⁷ and P = 9 × 10⁻³, respectively). For Zone I ROP, single-treatment success rates were 91.2% (95% CI: 83.6–96.9; n = 231) for bevacizumab, 78.3% (95% CI: 61.4–91.9; n = 100) for ranibizumab, and 65.9% (95% CI: 41.4–87.2; n = 158) for laser treatment. In this case, Bayesian network meta-analysis suggests that primary bevacizumab is associated with a significant 67% (95% CrI:10%–90%) reduction in retreatment risk compared with laser treatment.

Conclusions

Laser was associated with a lower rate of retreatment than ranibizumab in type 1 ROP (Zones I and II combined), while bevacizumab was associated with a lower rate of retreatment than laser in Zone I ROP. Aflibercept and bevacizumab demonstrate longer duration of action than ranibizumab for ROP.

中文翻译：

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贝伐珠单抗、雷珠单抗、阿柏西普和激光治疗早产儿视网膜病变后再治疗率的网络荟萃分析

话题

比较贝伐珠单抗、雷珠单抗、阿柏西普和激光治疗作为早产儿视网膜病变 (ROP) 主要疗法的再治疗率。

临床相关性

抗 VEGF 药物越来越多地用作 ROP 的主要治疗方法，并且与激光治疗后路疾病相比可能提供更好的结果。缺乏不同抗 VEGF 之间的头对头比较。

方法

我们在 CENTRAL、Embase、MEDLINE 和 CINAHL 数据库中搜索截至 2022 年 3 月已报告的随机对照试验和非随机比较研究。我们纳入了使用贝伐珠单抗、雷珠单抗、阿柏西普或激光治疗 ROP 的研究，具有可比较的队列和治疗标准。研究通过推荐分级、评估、开发和评估框架进行评估，排除病例选择有偏倚、非随机病例对照或缺乏对照组的研究。比例的频率荟萃分析确定了每种模式的绝对初级再治疗率，贝叶斯网络荟萃分析比较了 1 型和 I 区 ROP 中的成对治疗。

结果

总共有 30 项研究（4686 只眼睛）被纳入网络荟萃分析。对于 1 型 ROP，激光的单次治疗成功率（即不需要进一步治疗的可能性）为 89.3%（95% 置信区间 [CI]：83.8%–93.8%；n = 1552），激光为 87.0%（95%贝伐珠单抗 CI：78.6%–93.8%；n = 2081），阿柏西普 80.7%（95% CI：62.0%–94.4%；n = 326），阿柏西普 74.0%（95% CI：62.7%–84.1%；n = 727) 对于雷珠单抗。贝叶斯网络荟萃分析表明，与雷珠单抗相比，激光治疗可使再治疗风险显着降低 62%（95% 可信区间 [CrI]：16%–83%），而在其他配对比较中未发现显着差异。主要阿柏西普（12.96 ± 0.47 周）和贝伐珠单抗（11.36 ± 0.P  = 7 × 10 ^-7和P  = 9 × 10 ^-3）。对于 I 区 ROP，贝伐珠单抗的单次治疗成功率为 91.2%（95% CI：83.6-96.9；n = 231），雷珠单抗为 78.3%（95% CI：61.4-91.9；n = 100），以及 65.9% (95% CI: 41.4–87.2; n = 158) 用于激光治疗。在这种情况下，贝叶斯网络荟萃分析表明，与激光治疗相比，主要贝伐珠单抗可使再治疗风险显着降低 67%（95% CrI：10%–90%）。

结论

在 1 型 ROP（I 区和 II 区合并）中，激光与雷珠单抗相比具有较低的再治疗率，而在 I 区 ROP 中，贝伐单抗与激光相比具有较低的再治疗率。对于 ROP，阿柏西普和贝伐珠单抗的作用持续时间比雷珠单抗更长。