Multicenter Uveitis Steroid Treatment (MUST) Trial

多中心葡萄膜炎类固醇治疗 (MUST) 试验

• 批准号: 8459385
• 负责人: Douglas A Jabs
• 金额: $ 33.51万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459385
• 关键词: Address; Adrenal Cortex Hormones; Adverse effects; Autoimmune Process; Blindness; Cataract; Choroidal Neovascularization; Clinical Management; Clinical Research; Clinical Treatment; Clinical Trials; Clinical Trials Network; Data; Disease; Effectiveness; Epidemiologic Studies; Epiretinal Membrane; Fluocinolone Acetonide; Future; Glaucoma; Goals; Group Structure; Humira; Immunosuppression; Immunosuppressive Agents; Implant; Inflammation; Instruction; Laboratories; Local Therapy; Lucentis; Monoclonal Antibodies; Oral; Outcomes Research; Patient Agents; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiologic Intraocular Pressure; Pilot Projects; Principal Investigator; Process; Randomized Controlled Clinical Trials; Refractory; Relative (related person); Research; Research Technics; Retinal Neovascularization; Rheumatoid Arthritis; Safety; San Francisco; Series; Steroids; Structure; Systemic Therapy; Treatment Efficacy; Triamcinolone Acetonide; Tumor Necrosis Factor-alpha; United States Food and Drug Administration; Uveitis; Vascular Endothelial Growth Factors; Vision; Work; adalimumab; cohort; comparative trial; compare effectiveness; effective therapy; evidence base; follow-up; high risk; human monoclonal antibodies; macular edema; primary outcome; ranibizumab; research study; standard care; treatment trial; trial comparing

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.

该提案的目标是建立一个能够参与多项临床试验的临床试验网络 葡萄膜炎及其并发症的治疗。澳门科技大学研究小组（RG）的结构已经建立 已经制定了临床试验的审查、批准和优先顺序的地点和流程。四 临床研究被提议作为所提议网络的初始活动，它代表了 该提案的具体目标。它们是： 1) 在最初的基础上继续当前的 MUST 试验后续行动 两年内确定主要结局，并持续 6 年。这项长期后续行动将使 必须 RG 评估两种治疗范式的长期后果： 皮质类固醇治疗 v. 皮质类固醇和免疫抑制的全身治疗； 2）比较 阿达木单抗（Humira(R)，雅培实验室，雅培公园，伊利诺伊州）（一种完全人源化药物）的相对有效性 TNF-a 单克隆抗体与传统免疫抑制剂治疗需要治疗的严重葡萄膜炎患者 免疫抑制药物治疗。阿达木单抗已获得美国食品和药物管理局的批准 (FDA) 用于治疗多种自身免疫或自身炎症疾病，例如类风湿性关节炎、 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） 比较眼周与玻璃体内皮质类固醇治疗黄斑水肿患者的效果 葡萄膜炎。眼周和玻璃体内皮质类固醇似乎对治疗黄斑部有效 葡萄膜炎患者出现水肿，但尚未进行比较试验。许多临床医生认为 对于这种适应症，玻璃体内注射皮质类固醇比眼周皮质类固醇更有效，但它们 副作用发生率也较高； 4) 比较玻璃体内注射雷珠单抗（Lucentis(R), Genentech Inc.，旧金山，加利福尼亚州），一种针对血管内皮生长因子的单克隆抗体，可用于玻璃体内 皮质类固醇用于治疗葡萄膜炎患者的难治性黄斑水肿。一项试点研究建议 雷珠单抗可有效治疗葡萄膜炎性黄斑水肿，并且可能具有 与皮质类固醇相比，眼部副作用更少。然而，两种治疗的相对疗效尚不清楚。 相关性（参见说明）： 非感染性葡萄膜炎与视力丧失率较高有关，通常需要长期治疗， 通常与口服皮质类固醇合用，并在有需要时补充免疫抑制剂（皮质类固醇- 节省）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，为这些病症的管理提供证据基础。