A Pilot Study of Etanercept in Dermatomyositis

依那西普治疗皮肌炎的初步研究

• 批准号: 6967855
• 负责人: ANTHONY Arnold AMATO
• 金额: $ 46.26万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967855
• 关键词: biopsy; blood chemistry; clinical research; clinical trials; combination therapy; dermatomyositis; drug adverse effect; drug screening /evaluation; electrocardiography; gene expression profiling; human subject; human therapy evaluation; immunosuppressive; longitudinal human study; muscle disorder chemotherapy; muscle function; muscle strength; nonsteroidal antiinflammatory agent; outcomes research; photon absorptiometry; prednisone; questionnaires

Dermatomyositis (DM) is one of the major subtypes of idiopathic inflammatory myopathy. Prednisone is the initial treatment of choice in most patients with DM. However, because of the high rate of patients with disabling weakness despite treatment with prednisone, the long-term side effects of prednisone, and the many side effects associated with other second-line immunosuppressive agents (e.g., methotrexate, azathioprine), better treatment options are needed. There is evidence that tumor necrosis factor-alpha (TNF-alpha) plays a role in the pathogenesis of DM. Thus, etanercept, which blocks TNF-alpha, is a logical drug to assess in DM. Etanercept has been associated with a number of side effects including an increased risk of infection, inducing other autoimmune diseases, and perhaps cancer. These risks may be further enhanced in DM in which the frequency of other autoimmune disorders (e.g., connective tissue disease) and malignancy are already increased. The goal of this pilot study will be to assess the safety and tolerability of etanercept in DM. We will perform a double-blind, placebo-controlled pilot study of etanercept in 40 patients with DM randomized in a 3:1 ratio to receive etanercept or placebo. All patients will be started on a standard dose of prednisone and tapering schedule. They will be followed for 1 year and we will assess various outcome variables recommended by the International Myositis Assessment Clinical Study Group (BVIACS). The primary aim of the study is to preliminarily assess the safety and tolerability of etancercept in patients with DM. We hypothesize that etancercept will be safe and well tolerated in this population. The second aim is to assess the safety and tolerability of prednisone in the dosing schedule we propose to use. We hypothesize that most patients will be able tolerate the reduction of the prednisone dosage but most will not be able to be completely weaned off the medication. We believe we will find a relationship between prednisone dosage and its related side effects. The third aim of the study is to assess the variability, reliability, and responsiveness of the outcome measures recommended by IMACS using this pilot study of etanercept as the vehicle. The information gained from this study is necessary in order to design larger therapeutic trials of etanercept and other agents in DM.

皮肌炎是特发性炎症性肌病的主要亚型之一。泼尼松是大多数糖尿病患者的首选初始治疗。然而，由于尽管用泼尼松治疗，但致残性虚弱的患者的比例很高，泼尼松的长期副作用以及与其他二线免疫抑制剂相关的许多副作用（例如，甲氨蝶呤、硫唑嘌呤），需要更好的治疗选择。有证据表明，肿瘤坏死因子-α（TNF-α）在糖尿病的发病机制中发挥作用。因此，阻断TNF-α的依那西普是评估DM的合理药物。依那西普与许多副作用有关，包括感染风险增加，诱导其他自身免疫性疾病，可能还有癌症。这些风险可能在DM中进一步增强，其中其他自身免疫性疾病（例如，结缔组织病）和恶性肿瘤的发病率已经增加。本初步研究的目的是评估依那西普治疗DM的安全性和耐受性。我们将在40名DM患者中进行依那西普的双盲、安慰剂对照的初步研究，这些患者以3：1的比例随机接受依那西普或安慰剂治疗。所有患者都将开始接受标准剂量的泼尼松和逐渐减少的时间表。他们将被随访1年，我们将评估国际肌炎评估临床研究组（BVIACS）推荐的各种结果变量。本研究的主要目的是初步评估依那西普在糖尿病患者中的安全性和耐受性。我们假设依坦西普在该人群中安全且耐受性良好。第二个目的是评估我们建议使用的泼尼松给药方案的安全性和耐受性。我们假设大多数患者能够耐受泼尼松剂量的减少，但大多数患者不能完全停用药物。我们相信我们会发现泼尼松剂量与其相关副作用之间的关系。本研究的第三个目的是使用依那西普作为媒介物的初步研究，评估IMACS推荐的结局指标的变异性、可靠性和反应性。从本研究中获得的信息对于设计更大规模的依那西普和其他药物治疗DM的试验是必要的。