Vader Maartje J C, Schauwvlieghe Ann-Sofie M E, Verbraak Frank D, Dijkman Greetje, Hooymans Johanna M M, Los Leonoor I, Zwinderman Aeilko H, Peto Tunde, Hoyng Carel B, van Leeuwen Redmer, Vingerling Johannes R, Moll Annette C, van Lith-Verhoeven Janneke J C, Dijkgraaf Marcel G W, Schlingemann Reinier O
Department of Ophthalmology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Ophthalmology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Ophthalmol Retina. 2020 Aug;4(8):777-788. doi: 10.1016/j.oret.2020.02.008. Epub 2020 Feb 27.
To generate conclusive evidence regarding the noninferiority of intravitreal bevacizumab compared with ranibizumab in patients with diabetic macular edema (DME).
Comparative, randomized, double-masked, multicenter, noninferiority clinical trial.
Eligible patients were older than 18 years, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin of less than 12%, central area thickness of more than 325 μm, and visual impairment from DME with a best-corrected visual acuity (BCVA) between 24 letters and 78 letters.
From June 2012 through February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n = 86) or 0.5 mg ranibizumab (n = 84).
Primary outcome was change in BCVA from baseline to month 6 compared between the 2 treatment arms. The noninferiority margin was 3.5 letters.
The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months of follow-up; BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the 2-sided 90% confidence interval (CI) was -3.626 letters, exceeding the noninferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared with bevacizumab (64.2±104.2 μm). In a post hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, and central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared with the bevacizumab arm. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms.
Based on change in BCVA from baseline to month 6, the noninferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomic outcomes with ranibizumab. Our study confirmed the potential differential efficacy of anti-vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities.
获取关于玻璃体内注射贝伐单抗与雷珠单抗治疗糖尿病性黄斑水肿（DME）患者的非劣效性的确凿证据。
比较性、随机、双盲、多中心、非劣效性临床试验。
符合条件的患者年龄大于18岁，诊断为1型或2型糖尿病，糖化血红蛋白低于12%，中心区厚度超过325μm，且因DME导致视力受损，最佳矫正视力（BCVA）在24个字母至78个字母之间。
从2012年6月至2018年2月，共170名参与者被随机分配接受6次每月一次的注射，其中86名接受1.25mg贝伐单抗，84名接受0.5mg雷珠单抗。
主要结局是比较两个治疗组从基线到第6个月BCVA的变化。非劣效性界值为3.5个字母。
随访6个月后，治疗组之间平均BCVA的差异为有利于雷珠单抗的1.8个字母；贝伐单抗组BCVA改善了4.9±6.7个字母，雷珠单抗组改善了6.7±8.7个字母。双侧90%置信区间（CI）的下限为-3.626个字母，超过了3.5个字母的非劣效性界值。与贝伐单抗（64.2±104.2μm）相比，雷珠单抗使中心区厚度下降更多（138.2±114.3μm）。在一项事后亚组分析中，基线时BCVA较差（≤69个字母）的参与者使用贝伐单抗时BCVA改善了6.7±7.0个字母，使用雷珠单抗时改善了10.4±10.0个字母，且该亚组中雷珠单抗组的中心区厚度下降明显多于贝伐单抗组。基线时初始BCVA较好（≥70个字母）的参与者在治疗组之间的BCVA或光学相干断层扫描（OCT）结果上未显示出差异。
基于从基线到第6个月BCVA的变化，未证实1.25mg贝伐单抗相对于0.5mg雷珠单抗的非劣效性。仅基线时BCVA较低的患者亚组使用雷珠单抗显示出更好的视力和解剖学结局。我们的研究证实了抗血管内皮生长因子药物在治疗DME中的潜在差异疗效以及不同基线视力患者组之间的反应差异。
