Competitive Renewal for Multicenter Uveitis Steroid Treatment (MUST) Trial

描述（由申请人提供）：本提案的目标是建立一个临床试验网络，能够参与葡萄膜炎及其并发症治疗的多项临床试验。MUST研究小组（RG）结构已经到位，并且已经制定了审查、批准和确定临床试验优先顺序的流程。四项临床研究被提议作为提议网络的初始活动，它们代表了提议的具体目标。这些是：1)在最初确定主要结局的两年之后，继续目前的MUST试验随访6年。这项长期随访将使MUST RG能够评估两种治疗模式的长期后果：局部皮质类固醇治疗与皮质类固醇和免疫抑制的全身治疗；2)比较阿达木单抗（Humira）的相对疗效。雅培公司。艾伯特公园。IL)。针对需要免疫抑制药物治疗的严重葡萄膜炎患者的TNF-a的全人源单克隆抗体。阿达木单抗已经被美国食品和药物管理局（FDA）批准用于治疗几种自身免疫性或自身炎症性疾病，如类风湿关节炎，初步数据表明，它作为一种皮质类固醇保留剂对葡萄膜炎患者有效；3)比较眼周与玻璃体内皮质类固醇治疗葡萄膜炎患者黄斑水肿的疗效。眼周和玻璃体内皮质类固醇似乎对葡萄膜炎患者黄斑水肿的治疗有效，但没有进行比较试验。许多临床医生认为，对于这种适应症，玻璃体内皮质类固醇比眼周皮质类固醇更有效，但它们也有更高的副作用率；4)比较玻璃体内雷尼单抗（Lucentis(R)）。基因科技公司，旧金山。CA)。一种针对血管内皮生长因子的单克隆抗体，用于治疗葡萄膜炎患者难治性黄斑水肿。一项初步研究表明，雷尼单抗在治疗葡萄膜性黄斑水肿方面是有效的，并且可能比皮质类固醇具有更少的眼部副作用。然而，两种治疗方法的相对疗效尚不清楚。

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a clinical trials network capable of engaging in several clinical trials of the treatments of uveitis and its complications. The MUST Research Group (RG) structure already is in place, and processes have been developed for review, approval, and prioritization of clinical trials. Four clinical research studies are proposed as the initial activities of the proposed network, which represent the specific aims of the proposal. These are: 1) To continue the current MUST Trial follow-up past the original two-year determination of the primary outcome for an additional 6 years. This long-term follow-up will enable the MUST RG to evaluate the long-term consequences of the two treatment paradigms: regional corticosteroid treatment v. systemic therapy with corticosteroids and immunosuppression; 2) To compare the relative effectiveness of adalimumab (Humira(R). Abbott Laboratories. Abbott Park. IL). a fully human monoclonal antibody to TNF-a v. conventional immunosuppression for patients with severe uveitis requiring immunosuppressive drug therapy. Adalimumab already is approved by the US Food and Drug Administration (FDA) for the treatment of several autoimmune or autoinflammatory diseases, such as rheumatoid arthritis, and preliminary data suggest that it is effective as a corticosteroid-sparing agent in patients with uveitis; 3) To compare periocular v. intravitreal corticosteroids for the treatment of macular edema in patients with uveitis. Both periocular and intravitreal corticosteroids appear to be effective for the treatment of macular edema in patients with uveitis, but no comparative trials have been performed. Many clinicians believe that intravitreal corticosteroids are more effective than periocular corticosteroids for this indication, but that they also have higher rates of side effects; and 4) To compare intravitreal ranibizumab (Lucentis(R). Genentech Inc., San Francisco. CA). a monoclonal antibody to vascular endothelial growth factor, to intravitreal corticosteroids for the treatment of refractory macular edema in patients with uveitis. A pilot study suggested that ranibizumab was effective in the treatment of uveitic macular edema and that potentially it may have less ocular side effects than corticosteroids. However, the relative efficacy of the two treatments is unknown. RELEVANCE: Non-infectious uveitis is associated with high rates of visual loss and usually requires long-term therapy, often with oral corticosteroids, supplemented, when indicated, by immunosuppressive (corticosteroid- sparing) drugs. Visual loss often is caused by structural complications, e.g.. macular edema. We propose to carry out a series of clinical studies to provide an evidence base for the management of these conditions.