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

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.

项目概要/摘要 葡萄膜炎是一组以眼内炎症为特征的疾病。 在美国导致失明的第五大原因，治疗它们的估计费用与治疗类似 非传染性中间型、后型和全葡萄膜病变的视力下降率最高。 损失，通常用口服皮质类固醇和免疫抑制剂治疗。 治疗（必须）试验（一项随机、比较有效性试验，比较了 2 种治疗方法 这些疾病的范例，皮质类固醇和免疫抑制的全身治疗与局部治疗 治疗[氟轻松丙酮植入物]），后续研究证明了该疗法的优越性 就长期视力结果而言，局部眼部方法的系统方法基本上没有 全身治疗组中全身副作用的增加是全身治疗成功的关键之一。 88% 的参与者进行全身免疫抑制，同时将泼尼松剂量逐渐减少至<7.5 mg/天， 相对安全剂量最常用的药物是硫唑嘌呤、甲氨蝶呤、麦考酚酯、 环孢素和他克莫司较少使用。 由于担心潜在的恶性肿瘤风险增加，现有数据表明单一药物。 常规的非烷化剂免疫抑制药物可有效控制炎症 同时允许约 40-55% 的患者将泼尼松剂量逐渐减少至 <10 mg/天，因此通常采用联合治疗； 需要最大限度地减少泼尼松的每日剂量，因为这会增加患心血管疾病的风险。 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，全人源抗 TNF-α 药物上市。 单克隆抗体阿达木单抗已获得美国食品和药物管理局（FDA）批准用于 抗 TNF-α 单克隆抗体疗法彻底改变了葡萄膜炎的治疗。 风湿性疾病主要是由于其与传统的疾病修饰抗药相比具有优越的功效 风湿病药物。VISUAL III 的数据，两项 3 期试验的扩展导致 FDA 批准了 阿达木单抗治疗葡萄膜炎，表明阿达木单抗可能优于传统药物 免疫抑制，约 75% 的人使用 <5 毫克/天的泼尼松剂量控制了炎症 ADalimumab 与传统的葡萄膜炎免疫抑制治疗持续了 1 年。 (ADVISE) 试验是一项随机、比较有效性试验，将阿达木单抗与传统药物进行比较 对非感染性、中间型、后型和全葡萄膜炎患者进行免疫抑制。 结果是在随机分组后 6 个月内成功将泼尼松逐渐减少至 <7.5 mg/天的能力，同时 维持炎症的控制包括停用泼尼松。 炎症控制 1 年、视力、葡萄膜炎并发症及其治疗。