A Pilot Study of Etanercept in Dermatomyositis

皮肌炎（DM）是特发性炎性肌病的主要亚型之一。强的松是大多数糖尿病患者的初始治疗选择。然而，由于强的松治疗后致残性虚弱的患者比例很高，强的松的长期副作用，以及与其他二线免疫抑制剂（如甲氨蝶呤、硫唑嘌呤）相关的许多副作用，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起作用。因此，依那西普阻断tnf - α，是评估糖尿病的合理药物。依那西普与许多副作用相关，包括感染风险增加，诱导其他自身免疫性疾病，甚至可能是癌症。在其他自身免疫性疾病（如结缔组织疾病）和恶性肿瘤的发生频率已经增加的糖尿病中，这些风险可能进一步增强。本初步研究的目的是评估依那西普治疗糖尿病的安全性和耐受性。我们将在40名糖尿病患者中进行一项双盲、安慰剂对照的依那西普初步研究，以3:1的比例随机分配接受依那西普或安慰剂。所有患者将开始使用标准剂量的强的松并逐渐减少剂量。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坦塞普在糖尿病患者中的安全性和耐受性。我们假设依坦塞普在这一人群中是安全且耐受性良好的。第二个目的是评估强的松在我们建议使用的给药方案中的安全性和耐受性。我们假设大多数患者能够忍受泼尼松剂量的减少，但大多数患者无法完全戒掉这种药物。我们相信我们会发现强的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评估IMACS推荐的以依那西普为载体的结果测量的可变性、可靠性和响应性。从这项研究中获得的信息对于设计依那西普和其他药物治疗糖尿病的更大规模试验是必要的。

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.