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

描述(由申请人提供)：这项研究的目标是在一项掩蔽的随机试验中，确定哪种免疫抑制疗法-甲氨蝶呤或霉酚酸酯-作为一线非皮质类固醇非感染性葡萄膜炎的治疗更有效。在美国和全世界，葡萄膜炎是导致视力丧失和发病率的重要原因。由于长期使用皮质类固醇治疗会产生大量局部和全身副作用，其他免疫抑制疗法经常被用来作为皮质类固醇保留药，用于那些无法通过减少皮质类固醇来成功控制炎症的患者。这些药物包括抗代谢药物、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一种有效的初始皮质类固醇节约剂极其重要。 当需要非皮质类固醇治疗时，最常用的两种一线免疫抑制剂是抗代谢药物甲氨蝶呤和霉酚酸酯；其他类别的药物，如生物制剂，通常保留给难治性病例，在这些病例中，其他治疗因其成本和潜在的危险长期副作用而失败。通常的做法是，需要非类固醇药物的患者首先用甲氨蝶呤治疗，如果治疗失败，再改用霉酚酸酯。然而，回顾病例系列的结果表明，葡萄膜炎患者可能更有可能实现可控性炎症并耐受霉酚酸酯治疗。目前还没有前瞻性的随机对照试验来系统地确定哪种抗代谢药在临床上更有效，作为最初的类固醇非激素治疗，也没有证据依据来决定如果患者一种抗代谢药失败，是否改用另一种抗代谢药或转向另一类免疫抑制剂。 在这项多中心、隐蔽、随机的试验中，我们将评估甲氨蝶呤和霉酚酸酯作为非感染性葡萄膜炎患者的非激素初始治疗的安全性和有效性，以及在初始治疗失败后转换剂的临床疗效。患者将在加州大学旧金山分校、俄亥俄州立大学和阿拉文德眼科医院登记。

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.