ADALIMUMAB VERSUS CONVENTIONAL IMMUNOSUPPRESSION FOR UVEITIS (ADVISE) TRIAL

阿达木单抗与传统免疫抑制疗法治疗葡萄膜炎（建议）试验

• 批准号: 10867950
• 负责人: Douglas A Jabs
• 金额: $ 30.24万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10867950
• 关键词: Adrenal Cortex Hormones; Alkylating Agents; Azathioprine; Blindness; Chlorambucil; Chronic; Collection; Combined Modality Therapy; Coupled; Cyclophosphamide; Cyclosporine; Data; Diabetic Retinopathy; Disease; Disease-Modifying Second-Line Drugs; Dose; Drug usage; Fluocinolone Acetonide; Follow-Up Studies; Human; Immunosuppression; Immunosuppressive Agents; Implant; Inflammation; Malignant Neoplasms; Methotrexate; Monoclonal Antibodies; Monoclonal Antibody Therapy; Mycophenolate; Oral; Outcome; Participant; Patients; Prednisone; Randomized; Rheumatism; Risk; Steroids; Systemic Therapy; TNF gene; Tacrolimus; United States Food and Drug Administration; Uveitis; Vision; Visual; Visual Acuity; adalimumab; cardiovascular disorder risk; comparative effectiveness trial; comparative efficacy; cost estimate; follow-up; mortality; phase III trial; primary outcome; secondary outcome; side effect; success; treatment trial; trial comparing

PROJECT SUMMARY The uveitides are a collection of diseases characterized by intraocular inflammation. Collectively, they are the 5th leading cause of blindness in the US, and the estimated cost of treating them is similar to that of treating diabetic retinopathy. Non-infectious intermediate, posterior, and panuveitides have the highest rates of visual loss and typically are treated with oral corticosteroids and immunosuppression. The Multicenter Uveitis Steroid Treatment (MUST) Trial (a randomized, comparative effectiveness trial, which compared 2 treatment paradigms for these diseases, systemic therapy with corticosteroids and immunosuppression vs. regional therapy [the fluocinolone acetonide implant]), and Follow-up Study demonstrated the superiority of the systemic approach to the regional ocular approach in terms of long-term visual outcomes with essentially no increase in systemic side effects in the systemic group. One key to systemic therapy’s success was the use of systemic immunosuppression in 88% of participants, coupled with tapering the prednisone to <7.5 mg/day, a relatively safe dose. The drugs used most often used are azathioprine, methotrexate, mycophenolate, cyclosporine, and tacrolimus. The alkylating agents, cyclophosphamide and chlorambucil, are used less often because of concerns about potential increased malignancy risk. Available data suggest that single-agent conventional, non-alkylating-agent, immunosuppressive drugs are effective in controlling the inflammation while permitting tapering prednisone to <10 mg/day in ~40-55% of patients; hence, combination therapy often is needed. Minimizing the daily dose of prednisone is important, as the risk of cardiovascular disease and mortality increases with the cumulative dose of oral corticosteroids. In June 2016, the fully-human, anti-TNF-α monoclonal antibody, adalimumab, was approved by the US Food and Drug Administration (FDA) for the treatment of uveitis. Anti-TNF-α monoclonal antibody therapy has revolutionized the management of the rheumatic diseases largely due to its superior efficacy compared to conventional Disease Modifying Anti- Rheumatic Drugs. Data from VISUAL III, the extension of the two phase 3 trials that led to the FDA approval of adalimumab for the treatment of uveitis, suggest that adalimumab may be superior to conventional immunosuppression, as ~75% of participants had controlled inflammation with prednisone doses <5 mg/day sustained through 1 year of follow-up. The Adalimumab vs. Conventional Immunosuppression for Uveitis (ADVISE) Trial is a randomized, comparative effectiveness trial comparing adalimumab to conventional agent immunosuppression for patients with non-infectious, intermediate, posterior, and panuveitides. The primary outcome is the ability to successfully taper prednisone to <7.5 mg/day by 6 months after randomization while maintaining control of the inflammation. Secondary outcomes include prednisone discontinuation with inflammation control by 1 year, visual acuity, and incident complications of uveitis and its treatment.

项目总结 葡萄膜炎是一组以眼内炎症为特征的疾病。总而言之，他们是 美国第五大致盲原因，估计治疗费用与治疗费用相似 糖尿病视网膜病变。非感染性中间、后部和全葡萄膜炎的视力发生率最高。 通常使用口服皮质类固醇和免疫抑制药物治疗。多中心葡萄膜炎类固醇 治疗(必须)试验(一项随机比较有效性试验，比较两种治疗方法 这些疾病的范例，使用皮质类固醇和免疫抑制的系统治疗与局部对照 治疗[氟康奈德植入物])，以及随访研究证明了该方法的优越性 从长期视觉结果的角度对区域眼球切入法进行系统的研究，基本上没有 全身组的全身副作用增加。系统疗法成功的一个关键是使用 88%的参与者出现全身免疫抑制，同时将泼尼松的剂量减少到7.5毫克/天， 相对安全的剂量。最常用的药物有硫唑嘌呤、甲氨蝶呤、霉酚酸酯、 环孢素和他克莫司。烷化剂环磷酰胺和克百威使用频率较低。 因为担心潜在的恶性风险增加。现有数据表明，单一代理人 传统的、非烷基化的、免疫抑制药物在控制炎症方面是有效的。 同时允许约40-55%的患者每天减少泼尼松至10毫克；因此，联合治疗通常 是必要的。尽量减少泼尼松的每日剂量是很重要的，因为心血管疾病和 死亡率随着口服皮质类固醇累积剂量的增加而增加。2016年6月，全人、抗肿瘤坏死因子-α 单抗adalimumab被美国食品和药物管理局(FDA)批准用于治疗 葡萄膜炎的治疗。抗肿瘤坏死因子-α单抗疗法彻底改变了对 风湿性疾病很大程度上是因为它的疗效优于传统的疾病修补剂 风湿药。来自VISUAL III的数据，这是导致FDA批准的两个阶段3试验的扩展 阿达利单抗治疗葡萄膜炎，提示阿达利单抗可能优于常规 免疫抑制，因为约75%的参与者每天服用5毫克强的松控制了炎症 持续1年的随访。阿达利单抗与传统免疫抑制剂治疗葡萄膜炎的比较 (COVISE)试验是一项比较阿达利玛单抗和常规药物有效性的随机对照试验。 免疫抑制适用于非感染性、中间性、后遗症和全尿毒症患者。初级阶段 结果是，在随机试验后6个月内，泼尼松能够成功地减少到7.5毫克/天，而 保持炎症的控制。次要结果包括强的松停用与 炎症控制1年，视力，葡萄膜炎并发症及其治疗。