Multicenter Uveitis Steroid Treatment (MUST) Trial

这项建议的目标是发展一个临床试验网络，能够从事几项临床试验 葡萄膜炎及其并发症的治疗。必须研究小组(RG)的结构已经在 已经为临床试验的审查、批准和优先顺序制定了程序。四 临床研究研究被提议作为拟议网络的初始活动，代表 提案的具体目标。这些是：1)要继续目前的审判，必须跟踪原来的情况 两年内确定主要结果，再延长6年。这一长期跟踪将使 评估两种治疗模式长期后果的必须RG：地区性 皮质类固醇治疗与全身皮质类固醇治疗和免疫抑制；2)比较 阿达利单抗(Humira(R)，雅培实验室，伊利诺伊州雅培公园)的相对有效性，完全人类 抗肿瘤坏死因子-α的单抗V.重症葡萄膜炎患者的常规免疫抑制 免疫抑制药物治疗。阿达利马已经得到美国食品和药物管理局的批准 (FDA)用于治疗几种自身免疫性或自体炎性疾病，如类风湿性关节炎， 初步数据表明，它是葡萄膜炎患者的一种有效的皮质类固醇节约剂；3) 眼周与玻璃体内糖皮质激素治疗黄斑水肿的疗效比较 葡萄膜炎。眼周和玻璃体内皮质类固醇似乎对治疗黄斑都有效。 葡萄膜炎患者出现水肿，但尚未进行对照试验。许多临床医生认为 对于这一适应症，玻璃体内皮质类固醇比眼周皮质类固醇更有效，但他们 也有更高的副作用发生率；以及4)玻璃体内注射雷尼比珠单抗(Lucentis(R)，Genentech Inc.，旧金山，CA)，抗血管内皮生长因子的单抗，用于玻璃体内 糖皮质激素治疗葡萄膜炎患者难治性黄斑水肿。一项初步研究表明 雷尼比珠单抗在治疗葡萄膜黄斑水肿方面是有效的，而且可能有 眼部副作用比皮质类固醇少。然而，这两种疗法的相对疗效尚不清楚。 相关性(请参阅说明)： 非感染性葡萄膜炎与高视力损失率相关，通常需要长期治疗， 通常使用口服皮质类固醇，如果需要，辅以免疫抑制(皮质类固醇- 节制)毒品。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，为这些疾病的治疗提供证据基础。

The goal ofthis 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 ofthe proposed network, which represent the specific aims ofthe proposal. These are: 1) To continue the current MUST Trial follow-up past the original two-year determination ofthe primary outcome for an additional 6 years. This long-term follow-up will enable the MUST RG to evaluate the long-term consequences ofthe 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 ofthe two treatments is unknown. RELEVANCE (See instructions): 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 ofthese conditions.