本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(23)02577-1

摘要内容如下：

背景

玻璃体内注射高剂量阿柏西普（8 mg）可改善糖尿病性黄斑水肿（DMO）的治疗结果，因为与标准对照药物阿柏西普2 mg相比，所需的注射次数更少。我们报告了阿柏西普8 mg与2 mg在DMO患者中的疗效和安全性结果。

方法

Photon是一项随机、双盲、非劣效性的2/3期试验，在7个国家的138家医院和专业视网膜诊所进行。符合条件的患者是18岁或以上的成人，患有1型或2型糖尿病和中心参与的DMO。患者随机分配（1:2:1）每8周（2q8）玻璃体内注射阿柏西普2 mg，每12周（8q12）玻璃体内注射阿柏西普8 mg，或每16周（8q16）玻璃体内注射阿柏西普8 mg。从第16周开始，如果患者符合表明疾病活动的预先指定的剂量方案修改标准，则阿柏西普8 mg组的给药间隔缩短。主要终点是第48周时最佳矫正视力（BCVA）相对于基线的变化（4个字母的非劣效性界值）。疗效和安全性分析包括所有接受至少一剂研究治疗的随机分配患者。该试验在ClinicalTrials.gov（NCT04429503）上注册。

调查结果

在2020年6月29日至2021年6月28日期间，对970名患者进行了资格筛选。排除后，660名患者入选并随机分配接受阿柏西普8q12（n=329）、8q16（n=164）或2q8（n=167）；两名患者被错误地随机分配，没有接受治疗。658例（99.7%）患者接受治疗并纳入全分析集和安全性分析集（8q12 n=328，8q16 n=163，2q8 n=167）。患者平均年龄为62.3岁（SD 10.4）。401例（61%）患者为男性。471例（72%）患者为白人。与阿柏西普2q8相比，阿柏西普8q12和8q16的最佳矫正视力（BCVA）改善不明显（8q12组的平均基线变化为8.8个字母[SD 9.0]，8q16组的平均基线变化为7.9个字母[8.4]，2q8组的平均基线变化为9.2个字母[9.0]）。8q12和2q8之间的最小二乘均数差异为-0.57个字母（95%CI-2.26~1.13，非劣效性P值<0.0001），阿柏西普8q16和2q8之间的最小二乘均数差异为-1.44个字母（-3.27~0.39，非劣效性P值<0.0031）。各组研究眼中发生眼部不良事件的患者比例相似（8q12 n=104[32%]，8q16 n=48[29%]，2q8 n=46[28%]）。

解释

阿柏西普8 mg在延长给药间隔的情况下显示出疗效和安全性，并可降低DMO患者的治疗负担。

英文原文如下：

Abstracts

BACKGROUND  A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO.

METHODS  PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503).

FINDINGS  Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]).

INTERPRETATION  Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO.

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