PURPOSE To evaluate the durability of diabetic retinopathy (DR) improvements after a change in ranibizumab dosing from monthly to individualized pro re nata (PRN) therapy. DESIGN Pooled analysis of the open-label extension (OLE) of RIDE and RISE (clinicaltrials.gov identifiers, NCT00473382 and NCT00473330) patients with DR and diabetic macular edema (DME). PARTICIPANTS Patients who completed 36-month participation in RIDE and RISE and entered the OLE. METHODS In RIDE and RISE, patients (n = 759) were randomized 1:1:1 to ranibizumab 0.3 mg monthly, 0.5 mg monthly, or monthly sham injections with rescue macular laser available after 6 months, per protocol-specified criteria. After 24 months, sham patients crossed over to ranibizumab 0.5 mg monthly. After 36 months in the core studies, patients in the OLE (n = 500) could receive ranibizumab 0.5 mg PRN based on predefined DME re-treatment criteria. Diabetic retinopathy severity was evaluated photographically using the Early Treatment Diabetic Retinopathy Study DR severity scale. MAIN OUTCOME MEASURES Change in DR severity from months 36 to 48 by re-treatment status. RESULTS Among patients who entered the OLE, 121 of 500 (24%) did not require additional ranibizumab injections. Overall, 367 patients had evaluable DR at months 36 and 48. Among patients not requiring ranibizumab re-treatment from months 36 to 48 (88/367), 57% to 78%, 0% to 7%, and 22% to 36% experienced DR severity stability, 2-step or more improvement, and 2-step or more worsening, respectively. Among patients requiring ranibizumab re-treatment (279/367), 84% to 94%, 2%, and 3% to 14% experienced DR severity stability, 2-step or more improvement, and 2-step or more worsening, respectively. On average, vision improvements were maintained during the OLE regardless of change in DR severity. CONCLUSIONS Diabetic retinopathy severity improvements with ranibizumab were maintained in over 70% of OLE patients after switching from ranibizumab monthly to an individualized ranibizumab 0.5 mg PRN dosing regimen. Because approximately one third of OLE patients experienced DR worsening, careful monitoring should be part of the long-term management of patients with DR.

中文翻译：

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根据需要使用雷珠单抗改善糖尿病性视网膜病变的耐久性：RIDE和RISE研究的开放标签扩展。

目的评估兰尼单抗剂量从每月更改为个体前列腺（PRN）治疗后，糖尿病性视网膜病变（DR）改善的持久性。设计对患有DR和糖尿病性黄斑水肿（DME）的RIDE和RISE的开放标签扩展名（OLE）（clinicaltrials.gov标识符，NCT00473382和NCT00473330）进行汇总分析。参与者完成了36个月的RIDE和RISE参与并进入OLE的患者。方法在RIDE和RISE中，按照协议规定的标准，将患者（n = 759）按6：1的比例随机分配给雷尼珠单抗，每月0.3 mg，每月0.5 mg或每月一次用救援黄斑激光进行假性注射，6个月后可用。24个月后，假病人每月使用兰尼单抗0.5 mg。在核心研究中36个月后，OLE（n = 500）的患者可以接受兰尼单抗0。基于预定义的DME再治疗标准的5 mg PRN。使用早期治疗糖尿病性视网膜病变研究DR严重程度等级，通过照相评估糖尿病性视网膜病变的严重程度。主要观察指标根据再治疗状态，DR严重程度从第36个月更改为第48个月。结果在进入OLE的患者中，有500名患者中有121名（24％）不需要额外的兰尼单抗注射剂。总体而言，在第36和48个月中有367例患者具有可评估的DR。在36个月至48个月（88/367）不需要再次使用兰尼单抗的患者中，有57％到78％，0％到7％和22％到36％经历了DR严重程度的稳定性，2步或更多的改善以及2步或更多的恶化。在需要雷珠单抗再治疗的患者中（279/367），有84％至94％，2％和3％至14％的患者经历了DR严重性稳定性，两步或更多改善，和两步或更多步恶化。平均而言，在OLE期间，无论DR严重程度如何变化，都能保持视力改善。结论从兰尼单抗每月更换为个性化兰尼单抗0.5 mg PRN给药方案后，使用兰尼单抗的糖尿病视网膜病变严重程度得以维持，超过70％的OLE患者得以维持。因为大约三分之一的OLE患者经历了DR恶化，所以认真监测应该成为DR患者长期治疗的一部分。