ADalimumab Vs. conventional ImmunoSupprEssion for uveitis(ADVISE) Trial

阿达木单抗对比。

• 批准号: 10002234
• 负责人: Janet T. Holbrook
• 金额: $ 271.7万
• 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/10002234
• 关键词: Address; Adherence; Adrenal Cortex Hormones; Adverse event; Alkylating Agents; Ankylosing spondylitis; Antirheumatic Agents; Autoimmune Diseases; Azathioprine; Blindness; Chairperson; Child; Chlorambucil; Chronic; Clinical; Clinical Trials; Cohort Studies; Collection; Combined Modality Therapy; Coupled; Cyclophosphamide; Cyclosporine; Data; Data Set; Diabetic Retinopathy; Disease; Dose; Drug usage; Eye diseases; Fluocinolone Acetonide; Follow-Up Studies; Human; Immunosuppression; Immunosuppressive Agents; Implant; Infection; Inflammation; Malignant Neoplasms; Methotrexate; Monitor; Monoclonal Antibodies; Monoclonal Antibody Therapy; Mycophenolate; Oral; Outcome; Participant; Patients; Personal Communication; Pharmaceutical Preparations; Prednisone; Protocols documentation; Publications; Publishing; Randomized; Reading; Reporting; Research Personnel; Resources; Rheumatism; Rheumatoid Arthritis; Risk; Safety; Statistical Data Interpretation; Steroids; Structure; Systemic Therapy; TNF gene; Tacrolimus; Therapeutic immunosuppression; Time; United States; United States Food and Drug Administration; Uveitis; Vision; Visual; Visual Acuity; adalimumab; autoinflammatory; base; cardiovascular disorder risk; clinical center; cohort; comparative effectiveness trial; comparative efficacy; conventional therapy; cost estimate; data quality; follow-up; human monoclonal antibodies; mortality; outcome forecast; phase III trial; primary outcome; randomized placebo-controlled clinical trial; relative effectiveness; secondary outcome; side effect; success; treatment research; treatment trial; trial comparing; Address; Adherence; Adrenal Cortex Hormones; Adverse event; Alkylating Agents; Ankylosing spondylitis; Antirheumatic Agents; Autoimmune Diseases; Azathioprine; Blindness; Chairperson; Child; Chlorambucil; Chronic; Clinical; Clinical Trials; Cohort Studies; Collection; Combined Modality Therapy; Coupled; Cyclophosphamide; Cyclosporine; Data; Data Set; Diabetic Retinopathy; Disease; Dose; Drug usage; Eye diseases; Fluocinolone Acetonide; Follow-Up Studies; Human; Immunosuppression; Immunosuppressive Agents; Implant; Infection; Inflammation; Malignant Neoplasms; Methotrexate; Monitor; Monoclonal Antibodies; Monoclonal Antibody Therapy; Mycophenolate; Oral; Outcome; Participant; Patients; Personal Communication; Pharmaceutical Preparations; Prednisone; Protocols documentation; Publications; Publishing; Randomized; Reading; Reporting; Research Personnel; Resources; Rheumatism; Rheumatoid Arthritis; Risk; Safety; Statistical Data Interpretation; Steroids; Structure; Systemic Therapy; TNF gene; Tacrolimus; Therapeutic immunosuppression; Time; United States; United States Food and Drug Administration; Uveitis; Vision; Visual; Visual Acuity; adalimumab; autoinflammatory; base; cardiovascular disorder risk; clinical center; cohort; comparative effectiveness trial; comparative efficacy; conventional therapy; cost estimate; data quality; follow-up; human monoclonal antibodies; mortality; outcome forecast; phase III trial; primary outcome; randomized placebo-controlled clinical trial; relative effectiveness; secondary outcome; side effect; success; treatment research; treatment trial; trial comparing

PROJECT SUMMARY/ABSTRACT 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/摘要 葡萄象是以眼内炎症为特征的疾病集合。共同是 美国失明的第五主要原因以及治疗它们的估计成本类似于治疗 糖尿病性视网膜病。非感染的中间，后和甘韦赖特的视觉率最高 损失，通常用口服皮质类固醇和免疫抑制处理。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，比较了2种治疗 这些疾病的范式，皮质类固醇的全身治疗和免疫抑制与区域 治疗[氟乙醇酮乙醇植入物]），随访研究证明了 根据长期视觉结果的全身方法，基本上没有 全身群体的全身副作用增加。系统治疗成功的关键之一是使用 88％的参与者的全身免疫抑制，再加上泼尼松至<7.5 mg/天，A 相对安全的剂量。最常使用的药物是硫唑嘌呤，甲氨蝶呤，霉酚酸盐， 环孢菌素和他克莫司。烷基化剂，环磷酰胺和氯氨基核的使用较少 由于担心潜在的恶性风险。可用数据表明单位代理 常规的非烷基化药物，免疫抑制药物可有效控制炎症 约40-55％的患者允许将泼尼松逐渐减少到<10 mg/天；因此，组合疗法经常 需要。最小化泼尼松的每日剂量很重要，因为心血管疾病的风险和 死亡率随口服皮质类固醇的累积剂量而增加。 2016年6月，完全人类的抗TNF-α 单克隆抗体Adalimumab被美国食品药品监督管理局（FDA）批准 葡萄膜炎的治疗。抗TNF-α单克隆抗体疗法已彻底改变 风湿性疾病主要是由于其较高的效率与常规疾病的效率提高 风湿性药物。来自Visual III的数据，两期三期试验的扩展导致FDA批准 阿达木单抗治疗葡萄膜炎，表明阿达木单抗可能优于常规 免疫抑制，因为约有75％的参与者用泼尼松剂量<5 mg/天控制了注射 在1年的随访中持续。 Adalimumab vs。常规的葡萄膜炎免疫抑制 （建议）试验是一项比较阿达木单与常规代理的随机，比较有效性试验 非感染，中间，后和帕维替替替西替替替特的患者的免疫抑制。主要 结果是在随机化后6个月之前成功将泼尼松成功缩小到<7.5 mg/天的能力 保持对炎症的控制。次要结果包括泼尼松的终止 炎症控制1年，视力和葡萄膜炎的入射并发症及其治疗。