Competitive Renewal for Multicenter Uveitis Steroid Treatment (MUST) Trial

描述（由申请人提供）：本提案的目标是开发一个能够参与葡萄膜炎及其并发症治疗的多项临床试验的临床试验网络。MUST研究小组（RG）的结构已经到位，并且已经制定了临床试验的审查、批准和优先顺序的流程。四项临床研究被提议作为拟议网络的初始活动，这代表了该提案的具体目标。这些是：1）在最初确定主要结局的2年后，继续当前的MUST试验随访6年。该长期随访将使MUST RG能够评价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剂的全身治疗; 2）比较阿达木单抗（Humira（R））的相对有效性。雅培实验室。艾伯特公园。IL）。TNF-α的全人单克隆抗体与需要免疫抑制药物治疗的严重葡萄膜炎患者的常规免疫抑制。阿达木单抗已被美国食品药品监督管理局（FDA）批准用于治疗几种自身免疫性或自身炎症性疾病，如类风湿性关节炎，初步数据表明，它是一种有效的皮质类固醇节约剂在葡萄膜炎患者; 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。眼周和玻璃体内皮质类固醇似乎都能有效治疗葡萄膜炎患者的黄斑水肿，但没有进行比较试验。许多临床医生认为，玻璃体内皮质类固醇比眼周皮质类固醇对该适应症更有效，但它们也具有更高的副作用率;和4）为了比较玻璃体内雷珠单抗（Lucentis（R）.基因泰克公司，旧金山弗朗西斯科。CA）。抗血管内皮生长因子单克隆抗体，玻璃体内皮质类固醇治疗葡萄膜炎患者难治性黄斑水肿。一项初步研究表明，雷珠单抗在治疗葡萄膜炎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，这两种治疗方法的相对疗效尚不清楚。 相关性：非感染性葡萄膜炎与高视力丧失率相关，通常需要长期治疗，通常使用口服皮质类固醇，并在有指征时辅以免疫抑制（保留皮质类固醇）药物。视力丧失通常是由结构性并发症引起的，例如。黄斑水肿我们建议开展一系列临床研究，为这些疾病的管理提供证据基础。

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.