玻璃体内注射奈斯伐单抗（抗血管生成素 2）联合阿柏西普治疗糖尿病性黄斑水肿：RUBY 随机 2 期临床试验。

INTRAVITREAL NESVACUMAB (ANTIANGIOPOIETIN 2) PLUS AFLIBERCEPT IN DIABETIC MACULAR EDEMA: Phase 2 RUBY Randomized Trial.

机构信息

Retina Consultants of Texas (Retina Consultants of America), Houston, Texas.

Retina-Vitreous Associates Medical Group & University of Southern California/Keck School of Medicine in Los Angeles, Los Angeles, California.

出版信息

Retina. 2022 Jun 1;42(6):1111-1120. doi: 10.1097/IAE.0000000000003441. Epub 2022 Feb 22.

PURPOSE

The purpose of this study was to compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema.

METHODS

The eyes (n = 302) were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, Weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was rerandomized at Week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w, or HD combo q8w through Week 32.

RESULTS

Week 12 best-corrected visual acuity gains for LD and HD combo versus IAI were 6.8, 8.5, and 8.8 letters; Week 36 changes were similar. Central subfield retinal thickness reductions at Week 12 were -169.4, -184.0, and -174.6 µm (nominal P = 0.0183, HD combo vs. IAI); Week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were -210.4, -223.4, and -193.7 versus -61.9 µm (nominal P < 0.05). At Week 12, 13.3% and 21.3% versus 15.2% had ≥2-step Diabetic Retinopathy Severity Scale improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% versus 53.7% had complete foveal center fluid resolution. Safety was comparable across groups.

CONCLUSION

Nesvacumab + aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.

目的

本研究旨在比较玻璃体内注射奈维单抗（抗血管生成素 2）联合阿柏西普与玻璃体内注射阿柏西普（IAI）治疗糖尿病性黄斑水肿的疗效。

方法

本研究纳入 302 只眼，按 1:2:3 的比例随机分配至奈维单抗 3mg+阿柏西普 2mg（LD 联合治疗组）、奈维单抗 6mg+阿柏西普 2mg（HD 联合治疗组）或 IAI 2mg 治疗组，在基线、第 4 周和第 8 周时给药。LD 联合治疗组每 8 周（q8w）给药 1 次。HD 联合治疗组在第 12 周时重新随机分为 q8w 或每 12 周（q12w）1 次；IAI 组则每 8 周、每 12 周或 HD 联合治疗组 q8w 治疗至第 32 周。

结果

治疗第 12 周时，与 IAI 相比，LD 和 HD 联合治疗组的最佳矫正视力（BCVA）增益分别为 6.8、8.5 和 8.8 个字母；治疗第 36 周时，这种变化趋势仍然相似。治疗第 12 周时，中央视网膜厚度（CRT）较基线的减少值分别为-169.4μm、-184.0μm 和-174.6μm（名义 P=0.0183，HD 联合治疗组 vs. IAI 组）；治疗第 36 周时，LD 联合治疗组和 HD 联合治疗组 q8w 和 q12w 与 IAI 相比，CRT 减少值分别为-210.4μm、-223.4μm 和-193.7μm，而 IAI 组的 CRT 减少值为-61.9μm（名义 P<0.05）。治疗第 12 周时，LD 和 HD 联合治疗组分别有 13.3%和 21.3%的患者（vs. IAI 组，15.2%）的糖尿病视网膜病变严重程度评分（DRS）改善≥2 个等级，59.6%和 66.3%的患者（vs. IAI 组，53.7%）的黄斑中心凹完全无液。各组间的安全性无差异。