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

描述（由申请人提供）：本研究的目的是在一项设盲的随机试验中确定哪种免疫抑制疗法-甲氨蝶呤或霉酚酸酯-作为一线皮质类固醇保留剂治疗非感染性葡萄膜炎更有效。在美国和世界上，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局部和全身副作用的主机，其他免疫抑制疗法经常被用作皮质类固醇保留剂在患者谁不能成功地控制炎症与皮质类固醇减少。这些药物包括抗代谢药、钙调磷酸酶抑制剂、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保留剂极其重要。 当需要保留皮质类固醇治疗时，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，如生物制剂，通常保留用于其他治疗因其成本和潜在危险的长期副作用而失败的难治性病例。对于需要类固醇保留剂的患者，通常的做法是首先用甲氨蝶呤治疗，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达到控制炎症和耐受霉酚酸酯治疗。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作为最初的类固醇保留治疗在临床上更有效，也没有证据依据来决定是否换用另一种抗代谢药或在一种抗代谢药治疗失败后换用另一类免疫抑制剂。 在这项多中心、设盲、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转换药物的临床有效性。患者将在UCSF、OHSU和Aravind眼科医院入组。

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.