First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial

一线抗代谢药物作为类固醇节约治疗 (FAST) 葡萄膜炎试验

• 批准号: 8724947
• 负责人: NISHA ACHARYA
• 金额: $ 25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8724947
• 关键词: Adrenal Cortex Hormones; Adverse effects; Adverse event; Affect; Age; Alkylating Agents; Anatomy; Antimetabolites; Biology; Blindness; Calcineurin inhibitor; California; Case Series; Chronic; Clinical Trials; Clinical effectiveness; Developing Countries; Disease; Dose; Enrollment; Etiology; Event; Eye; Eye diseases; Foundations; Goals; Health Sciences; Hospitals; Immune; Immunosuppressive Agents; Implant; Incidence; India; Infection; Inflammation; Inflammatory; Intermediate Uveitis; Lead; Legal Blindness; Location; Masks; Mediating; Methotrexate; Morbidity - disease rate; Oral; Oregon; Panuveitis; Patients; Persons; Pharmaceutical Preparations; Prednisone; Prevalence; Protocols documentation; Quality of life; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Refractory; Relative (related person); Research; Rheumatology; Risk; Safety; San Francisco; Steroids; Therapeutic immunosuppression; Thick; Time; Topical Corticosteroids; Treatment Failure; United States; Universities; Uveitis; Visual Acuity; Work; age related; clinical efficacy; comparative effectiveness; cost; economic impact; evidence base; improved; macula; mycophenolate mofetil; primary outcome; prospective; randomized trial; secondary outcome; socioeconomics; success

DESCRIPTION (provided by applicant): The goal of this study is to establish which immuno-suppressive therapy - methotrexate or mycophenolate mofetil - is more effective as a first-line, corticosteroid-sparing agent for the treatment of non-infectious uveitis in a masked, randomized trial. Uveitis is a significant cause of vision loss and morbidity in the United States and the word. Due to the host of local and systemic side effects associated with long-term corticosteroid therapy, other immunosuppressive therapies are frequently used as corticosteroid-sparing agents in patients who are unable to successfully control inflammation with a reduction in corticosteroids. These include the antimetabolites, calcineurin inhibitors, alkylating agents, and biologic drugs. Cost and morbidity associated with uncontrolled inflammation make the selection of an effective initial corticosteroid- sparing agent extremely important. When corticosteroid-sparing therapy is required, two of the most commonly used first-line immunosuppressive agents are the antimetabolites methotrexate and mycophenolate mofetil; other classes of drugs such as biologics are typically reserved for refractory cases in which other treatments have failed because of their cost and potentially dangerous long-term side effects. It is common practice for patients requiring a steroid-sparing agent to be treated first with methotrexate and then switched to mycophenolate mofetil in the event of treatment failure. However, results from retrospective case series indicate that uveitis patients may be much more likely to achieve controlled inflammation and tolerate treatment with mycophenolate mofetil. There have been no prospective randomized, controlled trials to systematically determine which antimetabolite is more clinically effective as initial steroid-sparing therapy, and there is no evidence basis for deciding whether to switch to another antimetabolite or to move on to another class of immunosuppressives if patients fail one antimetabolite. In this multicenter, masked, randomized trial, we will evaluate the safety and efficacy of methotrexate and mycophenolate mofetil as initial corticosteroid-sparing therapy for patients with non-infectious uveitis, as well as evaluate the clinical effectiveness of switching agents aftr initial treatment failure. Patients will be enrolled at UCSF, OHSU, and Aravind Eye Hospital.

描述（由申请人提供）：本研究的目的是在一项隐蔽、随机试验中确定哪种免疫抑制疗法（甲氨蝶呤或吗替麦考酚酯）作为治疗非感染性葡萄膜炎的一线、省用皮质类固醇药物更有效。在美国和世界范围内，葡萄膜炎是视力丧失和发病的重要原因。由于与长期皮质类固醇治疗相关的一系列局部和全身副作用，对于无法通过减少皮质类固醇成功控制炎症的患者，经常使用其他免疫抑制疗法作为皮质类固醇节省药物。这些包括抗代谢药、钙调神经磷酸酶抑制剂、烷化剂和生物药物。与不受控制的炎症相关的成本和发病率使得选择有效的初始皮质类固醇节省剂极其重要。 当需要节省皮质类固醇治疗时，两种最常用的一线免疫抑制剂是抗代谢药甲氨蝶呤和吗替麦考酚酯；其他类别的药物（例如生物制剂）通常用于难治性病例，在这些病例中，其他治疗方法因其成本和潜在危险的长期副作用而失败。对于需要类固醇节省药物的患者来说，通常的做法是首先使用甲氨蝶呤治疗，然后在治疗失败时改用吗替麦考酚酯。然而，回顾性病例系列的结果表明，葡萄膜炎患者可能更有可能实现炎症控制并耐受吗替麦考酚酯治疗。目前还没有前瞻性随机对照试验来系统地确定哪种抗代谢药物作为初始类固醇保留治疗在临床上更有效，并且没有证据基础来决定是否改用另一种抗代谢药物或在患者对一种抗代谢药物无效时转向另一类免疫抑制剂。 在这项多中心、隐蔽、随机试验中，我们将评估甲氨蝶呤和吗替麦考酚酯作为非感染性葡萄膜炎患者初始皮质类固醇保留治疗的安全性和有效性，以及评估初始治疗失败后更换药物的临床有效性。患者将在 UCSF、OHSU 和 Aravind 眼科医院入组。