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 i s 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.
