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Abstract：
BACKGROUND: Key clinical guidelines recommend anti-vascular endothelial growth factor (VEGF) therapy as first-line treatment for visual impairment due to diabetic macular oedema (DMO). A systematic literature review (SLR) and network meta-analysis (NMA) were conducted comparing the relative efficacy of the anti-VEGF brolucizumab with a focused network of the most relevant comparator dosing regimens approved in countries other than the USA (aflibercept, ranibizumab). The safety and tolerability of brolucizumab were also assessed.
METHODS: A broad SLR was conducted to identify randomised controlled trials to ensure all relevant potential comparators were captured. Identified studies were refined to those appropriate for inclusion in the NMA. A Bayesian NMA was conducted comparing brolucizumab 6 mg (every 12 [Q12W]/every 8 weeks [Q8W]) with relevant aflibercept 2 mg and ranibizumab 0.5 mg regimens.
RESULTS: Fourteen studies were included in the NMA. At 1-year follow-up, the various aflibercept 2 mg and ranibizumab 0.5 mg regimens were mostly comparable with brolucizumab 6 mg Q12W/Q8W across key visual and anatomical outcomes, except brolucizumab 6 mg was favoured over ranibizumab 0.5 mg every 4 weeks (Q4W) for the change from baseline (CFB) in best-corrected visual acuity (BCVA), and BCVA loss/gain of pre-specified numbers of letters, and over ranibizumab 0.5 mg pro re nata for CFB in diabetic retinopathy severity scale, and retinal thickness. At year 2, where data were available, brolucizumab 6 mg showed similar results across efficacy outcomes versus all other anti-VEGFs. In most cases, discontinuation rates (all cause, and due to adverse events [AE]) and serious and overall rates of AEs excluding ocular inflammatory events were similar (in unpooled and pooled-treatment analyses) versus comparators.
CONCLUSIONS: Brolucizumab 6 mg Q12W/Q8W was comparable or superior to aflibercept 2 mg and ranibizumab 0.5 mg regimens for various visual and anatomical efficacy outcomes and discontinuation rates.
METHODS: A broad SLR was conducted to identify randomised controlled trials to ensure all relevant potential comparators were captured. Identified studies were refined to those appropriate for inclusion in the NMA. A Bayesian NMA was conducted comparing brolucizumab 6 mg (every 12 [Q12W]/every 8 weeks [Q8W]) with relevant aflibercept 2 mg and ranibizumab 0.5 mg regimens.
RESULTS: Fourteen studies were included in the NMA. At 1-year follow-up, the various aflibercept 2 mg and ranibizumab 0.5 mg regimens were mostly comparable with brolucizumab 6 mg Q12W/Q8W across key visual and anatomical outcomes, except brolucizumab 6 mg was favoured over ranibizumab 0.5 mg every 4 weeks (Q4W) for the change from baseline (CFB) in best-corrected visual acuity (BCVA), and BCVA loss/gain of pre-specified numbers of letters, and over ranibizumab 0.5 mg pro re nata for CFB in diabetic retinopathy severity scale, and retinal thickness. At year 2, where data were available, brolucizumab 6 mg showed similar results across efficacy outcomes versus all other anti-VEGFs. In most cases, discontinuation rates (all cause, and due to adverse events [AE]) and serious and overall rates of AEs excluding ocular inflammatory events were similar (in unpooled and pooled-treatment analyses) versus comparators.
CONCLUSIONS: Brolucizumab 6 mg Q12W/Q8W was comparable or superior to aflibercept 2 mg and ranibizumab 0.5 mg regimens for various visual and anatomical efficacy outcomes and discontinuation rates.
摘要：
背景：主要临床指南推荐抗血管内皮生长因子（VEGF）治疗作为糖尿病性黄斑水肿（DMO）所致视力损害的一线治疗。进行了系统文献综述（SLR）和网络荟萃分析（NMA），比较了抗VEGF布鲁单抗与美国以外国家批准的最相关的比较给药方案的聚焦网络的相对疗效（阿柏西普，雷珠单抗）。还评估了brolucizumab的安全性和耐受性。
方法：进行广泛的SLR以确定随机对照试验，以确保捕获所有相关的潜在比较者。已确定的研究被细化为适合纳入NMA的研究。进行了贝叶斯NMA，比较了6mg的brolucizumab（每12[Q12W]/每8周[Q8W]）与相关的阿柏西普2mg和雷珠单抗0.5mg方案。
结果：14项研究纳入了NMA。在1年的随访中，各种阿柏西普2mg和雷珠单抗0.5mg方案在主要视觉和解剖学结局方面与布罗珠单抗6mgQ12W/Q8W相当,除了在最佳矫正视力（BCVA）中相对于基线（CFB）的变化方面，每4周（Q4W）6mg的brolucizumab优于0.5mg的雷珠单抗，和BCVA预先指定的字母数的损失/收益，在糖尿病视网膜病变严重程度量表中，超过雷珠单抗0.5mg前再纳塔用于CFB，和视网膜厚度。在第二年，有数据的地方，与所有其他抗VEGF相比，布罗珠单抗6mg在疗效结局中显示相似的结果。在大多数情况下,停药率(所有原因，并且由于不良事件[AE]），并且不包括眼部炎症事件的AE的严重和总体发生率（在未合并和合并治疗分析中）与比较者相似。
结论：Brolucizumab6mgQ12W/Q8W在各种视觉和解剖学疗效结果和停药率方面与阿柏西普2mg和雷珠单抗0.5mg方案相当或更好。
方法：进行广泛的SLR以确定随机对照试验，以确保捕获所有相关的潜在比较者。已确定的研究被细化为适合纳入NMA的研究。进行了贝叶斯NMA，比较了6mg的brolucizumab（每12[Q12W]/每8周[Q8W]）与相关的阿柏西普2mg和雷珠单抗0.5mg方案。
结果：14项研究纳入了NMA。在1年的随访中，各种阿柏西普2mg和雷珠单抗0.5mg方案在主要视觉和解剖学结局方面与布罗珠单抗6mgQ12W/Q8W相当,除了在最佳矫正视力（BCVA）中相对于基线（CFB）的变化方面，每4周（Q4W）6mg的brolucizumab优于0.5mg的雷珠单抗，和BCVA预先指定的字母数的损失/收益，在糖尿病视网膜病变严重程度量表中，超过雷珠单抗0.5mg前再纳塔用于CFB，和视网膜厚度。在第二年，有数据的地方，与所有其他抗VEGF相比，布罗珠单抗6mg在疗效结局中显示相似的结果。在大多数情况下,停药率(所有原因，并且由于不良事件[AE]），并且不包括眼部炎症事件的AE的严重和总体发生率（在未合并和合并治疗分析中）与比较者相似。
结论：Brolucizumab6mgQ12W/Q8W在各种视觉和解剖学疗效结果和停药率方面与阿柏西普2mg和雷珠单抗0.5mg方案相当或更好。
