Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
Ophthalmology. 2020 Apr;127(4S):S135-S145. doi: 10.1016/j.ophtha.2020.01.029.
To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.
Multicenter, randomized clinical trial.
Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.
At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.
Mean change in visual acuity.
Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).
Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
描述雷珠单抗和贝伐单抗每月治疗与按需治疗持续 2 年的效果，并描述在每月治疗 1 年后转为按需治疗的影响。
多中心、随机临床试验。
在纳入的 1185 例新生血管性年龄相关性黄斑变性患者中，有 1107 例患者在第 2 年接受了随访。
在入组时，根据药物（雷珠单抗或贝伐单抗）和剂量方案（每月或按需）将患者分为 4 个治疗组。在第 1 年，最初接受每月治疗的患者被随机重新分配至每月或按需治疗，而不改变药物分配。
视力的平均变化。
在 2 年期间遵循相同方案的患者中，两种药物的视力平均提高幅度相似（贝伐单抗-雷珠单抗差值为-1.4 个字母；95%置信区间[CI]，-3.7 至 0.8；P=0.21）。与按需治疗相比，每月治疗的平均提高幅度更大（差值为-2.4 个字母；95%CI，-4.8 至-0.1；P=0.046）。无积液的比例从贝伐单抗按需治疗组的 13.9%到雷珠单抗每月治疗组的 45.5%不等（药物，P=0.0003；方案，P<0.0001）。从每月治疗转为按需治疗在第 2 年导致视力平均下降更大（-2.2 个字母；P=0.03），无积液的比例更低（-19%；P<0.0001）。两种药物的死亡率和动脉血栓栓塞事件发生率相似（P>0.60）。贝伐单抗的全身性严重不良事件发生率高于雷珠单抗（39.9%比 31.7%；调整后的风险比，1.30；95%CI，1.07-1.57；P=0.009）。大多数额外的事件之前都与血管内皮生长因子（VEGF）靶向全身治疗无关。
雷珠单抗和贝伐单抗在 2 年期间对视敏度的影响相似。无论在入组时还是在每月治疗 1 年后开始按需治疗，视力的提高幅度都较小。两种药物在死亡率或动脉血栓栓塞事件发生率方面没有差异。由于缺乏与 VEGF 抑制相关的特异性，贝伐单抗的严重不良事件发生率较高的原因尚不确定。
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