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）：这项研究的目的是确定哪种免疫抑制疗法 - 甲氨蝶呤或霉酚酸酯莫菲蒂尔 - 作为一线，皮质类固醇的剂，用于治疗在掩盖的，随机的随机试验中对非感染性葡萄炎的治疗。葡萄膜炎是美国和词的视力丧失和发病率的重要原因。由于与长期皮质类固醇疗法相关的局部和全身性副作用，其他免疫抑制疗法经常被用作无法成功控制炎症而减少皮质类固醇的患者中的皮质类固醇药物剂。这些包括抗代谢物，钙调神经酶抑制剂，烷基化剂和生物药物。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为重要。 当需要使用皮质类固醇的治疗疗法时，最常用的一线免疫抑制剂是甲氨蝶呤和霉酚酸酯莫菲替尔的两种最常用的免疫抑制剂。其他类别的药物（例如生物制剂）通常保留用于难治性的病例，在这些病例中，由于其成本和潜在危险的长期副作用，其他治疗方法失败了。对于需要先甲氨蝶呤治疗，然后在治疗衰竭的情况下，先用甲氨蝶呤治疗，然后切换到霉酚酸莫菲蒂，这是常见的做法。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受控的炎症并耐受霉酚酸莫菲蒂尔的治疗。尚无前瞻性随机，对照试验，可以系统地确定哪种抗代谢物在初始类固醇治疗疗法上在临床上更有效，并且如果患者失败，则没有证据表明是决定是否切换到另一种抗替代代谢物或进入另一种类别的免疫抑制剂。 在这项多中心，掩盖的随机试验中，我们将评估甲氨蝶呤和霉酚酸酯莫菲蒂尔作为非感染葡萄膜炎患者的初始皮质类固醇治疗疗法的安全性和功效，并评估开关剂AFTR初始治疗失败的临床有效性。患者将在UCSF，OHSU和Aravind眼科医院招收。