Multicenter Uveitis Steroid Treatment (MUST) Trial

描述(由申请人提供)：这项建议的目标是发展一个临床试验网络，能够从事葡萄膜炎及其并发症的治疗的几个临床试验。必须研究小组(RG)的结构已经到位，并且已经制定了临床试验的审查、批准和优先顺序的程序。四项临床研究研究被提议作为拟议网络的初始活动，它们代表了提议的具体目标。这些是：1)要继续目前的试验，必须在最初的两年初步结果确定之后再进行6年的后续试验。这项长期随访将使MASH RG能够评估两种治疗方案的长期结果：区域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，雅培公园，伊利诺伊州)的相对有效性；Adalimumab是一种完全人类的抗肿瘤坏死因子-a的单抗，对需要免疫抑制药物治疗的严重葡萄膜炎患者进行常规免疫抑制治疗。Adalimumab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，如类风湿性关节炎，初步数据表明，它作为葡萄膜炎患者的皮质类固醇节约剂是有效的；3)比较眼周和玻璃体内皮质类固醇治疗葡萄膜炎患者的黄斑水肿。眼周和玻璃体内的皮质类固醇似乎都能有效地治疗葡萄膜炎患者的黄斑水肿，但还没有进行对比试验。许多临床医生认为，在这一适应症上，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；以及4)比较玻璃体内雷尼比珠单抗(Lucentis(R)，Genentech Inc.，加利福尼亚州旧金山)和玻璃体内皮质类固醇治疗葡萄膜炎患者难治性黄斑水肿的疗效。一项初步研究表明，雷尼比珠单抗在治疗葡萄膜炎黄斑水肿方面有效，可能比皮质类固醇有更少的眼部副作用。然而，这两种疗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损失率相关，通常需要长期治疗，通常是口服皮质类固醇，必要时辅以免疫抑制(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，为这些疾病的治疗提供证据基础。

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.