A Pilot Study of Etanercept in Dermatomyositis

皮肌炎(DM)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治疗方法。然而，由于接受泼尼松治疗的患者致残性虚弱的比例很高，泼尼松的长期副作用，以及与其他二线免疫抑制剂(如甲氨蝶呤、硫唑嘌呤)相关的许多副作用，需要更好的治疗方案。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一定作用。因此，阻断肿瘤坏死因子-α的依那西普是治疗糖尿病的合乎逻辑的药物。依那西普与一些副作用有关，包括增加感染风险，引发其他自身免疫性疾病，可能还有癌症。这些风险在糖尿病中可能进一步增强，因为其他自身免疫性疾病(例如结缔组织病)和恶性肿瘤的频率已经增加。这项先导性研究的目标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、安慰剂对照的先导性研究，患者按3：1的比例随机接受依那西普或安慰剂治疗。所有患者都将开始服用标准剂量的泼尼松和逐渐减少的时间表。我们将对他们进行为期一年的随访，并评估国际肌炎评估临床研究小组(BVIACS)推荐的各种结果变量。该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。我们假设依那西普在该人群中是安全和耐受性良好的。第二个目的是在我们建议使用的给药方案中评估泼尼松的安全性和耐受性。我们假设大多数患者将能够耐受强的松剂量的减少，但大多数患者不能完全摆脱药物治疗。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。这项研究的第三个目的是以依那西普为载体，评估iMACS推荐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更大规模的依那西普和其他药物治疗糖尿病的治疗试验是必要的。

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.