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: 10238823
• 负责人: Douglas A Jabs
• 金额: $ 16.66万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238823
• 关键词: Address; Adrenal Cortex Hormones; Adverse event; Alkylating Agents; Ankylosing spondylitis; Anterior; Antirheumatic Agents; Autoimmune; Azathioprine; Blindness; Chlorambucil; Chronic; Clinical; Collection; Combined Modality Therapy; Coupled; Cyclophosphamide; Cyclosporine; Data; Diabetic Retinopathy; Disease; Dose; Drug usage; Fluocinolone Acetonide; Follow-Up Studies; Human; Immunosuppression; Immunosuppressive Agents; Implant; Inflammation; Malignant Neoplasms; Methotrexate; Monoclonal Antibodies; Monoclonal Antibody Therapy; Mycophenolate; Nature; Oral; Outcome; Panuveitis; Participant; Patients; Personal Communication; Pharmaceutical Preparations; Prednisone; Prognosis; Quality of life; Randomized; Rheumatism; Rheumatoid Arthritis; Risk; Site; Steroids; Structure; Systemic Therapy; TNF gene; Tacrolimus; United States; United States Food and Drug Administration; Uveitis; Vision; Visual; Visual Acuity; adalimumab; autoinflammatory; base; cardiovascular disorder risk; comparative effectiveness; comparative effectiveness trial; comparative efficacy; conventional therapy; cost effectiveness; cost estimate; effectiveness clinical trial; follow-up; human monoclonal antibodies; macular edema; mortality; phase III trial; primary outcome; relative effectiveness; secondary outcome; side effect; small molecule; success; treatment group; treatment research; treatment strategy; 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.

项目摘要 葡萄膜炎是以眼内炎症为特征的疾病的集合。总的来说，他们是 美国第五大致盲原因，治疗它们的估计费用与治疗 糖尿病视网膜病变非感染性中间型、后型和全葡萄膜炎的视力损害率最高， 通常用口服皮质类固醇和免疫抑制剂治疗。多中心葡萄膜炎类固醇 治疗（MUST）试验（一项随机、比较有效性试验，比较2种治疗方法 这些疾病的治疗模式，皮质类固醇和免疫抑制剂的全身治疗与局部治疗 治疗[醋酸氟轻松植入剂]），随访研究表明， 在长期视力结果方面，系统性方法与局部眼部方法相比， 全身组中全身副作用增加。全身治疗成功的一个关键是使用 88%的参与者全身免疫抑制，加上泼尼松逐渐减少至<7.5 mg/天， 相对安全的剂量。最常用的药物是硫唑嘌呤、甲氨蝶呤、霉酚酸酯， 环孢霉素和他克莫司。烷化剂环磷酰胺和苯丁酸氮芥的使用较少 因为担心潜在的恶性肿瘤风险增加。现有数据表明， 常规的非烷化剂免疫抑制药物在控制炎症方面是有效的 同时允许约40-55%的患者将泼尼松逐渐减少至<10 mg/天;因此，联合治疗通常 是必要的。最大限度地减少泼尼松的日剂量很重要，因为心血管疾病的风险和 死亡率随着口服皮质类固醇的累积剂量而增加。2016年6月，全人类抗TNF-α 单克隆抗体阿达木单抗已被美国食品和药物管理局（FDA）批准用于 治疗葡萄膜炎。抗TNF-α单克隆抗体治疗彻底改变了 风湿性疾病，主要是由于其上级疗效相比，传统的疾病修饰抗 风湿药。数据来自VISUAL III，这是导致FDA批准的两项3期试验的扩展， 阿达木单抗治疗葡萄膜炎，表明阿达木单抗可能上级常规治疗， 免疫抑制，因为约75%的参与者通过泼尼松剂量<5 mg/天控制了炎症 持续1年随访。阿达木单抗与常规免疫抑制剂治疗葡萄膜炎的比较 （ADVISE）试验是一项比较阿达木单抗与常规药物的随机、比较有效性试验 非感染性、中间型、后型和全葡萄膜炎患者的免疫抑制。主 结果是在随机化后6个月成功地将泼尼松逐渐减少至<7.5 mg/天的能力， 维持对炎症的控制。次要结局包括泼尼松停药， 1年内炎症控制、视力和葡萄膜炎的并发症及其治疗。