Retina Consultants of Houston, Houston, Texas.
Elman Retina Group, Baltimore, Maryland.
Ophthalmology. 2016 Aug;123(8):1716-1721. doi: 10.1016/j.ophtha.2016.04.004. Epub 2016 May 18.
To investigate the role of baseline demographics, disease characteristics, and treatment responses to ranibizumab during RIDE/RISE in predicting long-term treatment frequency with a criteria-based pro re nata (PRN) regimen during the open-label extension (OLE).
Pooled, retrospective, post hoc analysis from the phase III, randomized RIDE/RISE studies and subsequent OLE.
Five hundred patients enrolled in the OLE after completion of the 36-month RIDE/RISE studies.
Summary statistics of RIDE/RISE baseline characteristics and treatment responses were generated by PRN ranibizumab 0.5 mg annualized injection frequency in the OLE (0 and >7 annualized injections). Univariable regression and analysis of variance, and multivariable analysis of covariance were performed on the annualized number of ranibizumab injections administered during the OLE versus baseline characteristics and response to treatment during the RIDE/RISE studies.
Association of patient characteristics and responses to treatment during RIDE/RISE with the observed ranibizumab treatment burden during the OLE.
During the OLE, 121 patients required no treatment, 132 required >0 to ≤3 annualized injections, 159 required >3 to ≤7 annualized injections, and 88 required >7 annualized injections. Parameters identified in the multivariable analysis as related to the annualized number of injections included the total number of rescue focal macular lasers received during the core studies (P = 0.0203), central foveal thickness at baseline (P = 0.0002) and month 36 (P < 0.0001), fluorescein leakage area at month 36 (P = 0.0137), and glycated hemoglobin (HbA1c) levels at month 36 (P = 0.0054). Patients receiving 0 versus >7 annualized injections during the OLE had, on average, a shorter duration of diabetes and diabetic macular edema (DME) at baseline, were less likely to have proliferative diabetic retinopathy at baseline, received fewer rescue focal macular laser treatments, and were more likely to experience diabetic retinopathy severity scale improvement of ≥2 steps.
Patients who received less frequent injections during the RIDE/RISE OLE tended to have less advanced disease at baseline and responded better to initial ranibizumab treatment, suggesting that earlier anti-vascular endothelial growth factor treatment of center-involving DME with visual acuity loss may decrease long-term treatment burden.
研究 RIDE/RISE 中基线人口统计学、疾病特征和对雷珠单抗的治疗反应在预测开放标签扩展（OLE）中基于标准的个体化治疗（PRN）方案的长期治疗频率中的作用。
来自 III 期随机 RIDE/RISE 研究和随后的 OLE 的汇总、回顾性、事后分析。
在 RIDE/RISE 研究的 36 个月完成后，500 名患者入组 OLE。
通过 OLE 中 PRN 雷珠单抗 0.5mg 年注射频率（0 次和>7 次）生成 RIDE/RISE 基线特征和治疗反应的汇总统计数据。对 OLE 中每年注射雷珠单抗的次数与基线特征和 RIDE/RISE 研究期间的治疗反应进行单变量回归和方差分析，以及多变量协方差分析。
患者特征和 RIDE/RISE 期间治疗反应与 OLE 期间观察到的雷珠单抗治疗负担的关系。
在 OLE 期间，121 名患者无需治疗，132 名患者需要>0 至≤3 次年度注射，159 名患者需要>3 至≤7 次年度注射，88 名患者需要>7 次年度注射。多变量分析中与注射次数相关的参数包括核心研究期间接受的挽救性局部黄斑激光治疗总数（P=0.0203）、基线时（P=0.0002）和第 36 个月时（P<0.0001）的中央视网膜厚度、第 36 个月时的荧光素渗漏面积（P=0.0137）和糖化血红蛋白（HbA1c）水平（P=0.0054）。在 OLE 期间接受 0 次和>7 次年度注射的患者平均基线时糖尿病和糖尿病性黄斑水肿（DME）的持续时间更短，基线时更不可能患有增殖性糖尿病性视网膜病变，接受的挽救性局部黄斑激光治疗更少，并且更有可能出现糖尿病视网膜病变严重程度量表改善≥2 个等级。
在 RIDE/RISE OLE 中接受较少注射的患者在基线时病情往往不太严重，对初始雷珠单抗治疗的反应更好，这表明对伴有视力丧失的中心性 DME 进行早期抗血管内皮生长因子治疗可能会降低长期治疗负担。
