A Pilot Study of Etanercept in Dermatomyositis
A Pilot Study of Etanercept in Dermatomyositis
The purpose of the study is to obtain preliminary data regarding the safety and tolerability
 of etanercept in DM. In addition, we will use the study to assess the variability,
 reliability, and responsiveness of the core set of outcome measures recommended by IMACS. The
 study will be performed under the aegis of the Muscle Study Group (MSG), consisting of
 experienced investigators with an avid interest in myopathies. The ultimate goal of this
 pilot study will be to obtain necessary, prerequisite information important in designing
 future therapeutic trials of etanercept and other agents in patients with DM. The specific
 aims of the study are:

 Aim 1: To preliminarily assess the safety and tolerability of etanercept in patients with DM.

 Aim 2: To assess the safety and tolerability of prednisone in the dosing schedule we propose
 to use.

 Aim 3: To evaluate outcome measures recommended by IMACS and assess their variability,
 reliability, and responsiveness in order to facilitate the design of future therapeutic
 trials in the inflammatory myopathies.
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-a (TNF-a) plays a role in
 the pathogenesis of DM. Thus, etanercept, which blocks TNF-a, 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 newly
 diagnosed and untreated patients will be started on a standard dose of prednisone and
 tapering schedule. Refractory patients who have been or are currently being treated with
 prednisone, IVIG, or methotrexate can also participate. Subjects will be followed for 1 year
 and we will assess various outcome variables recommended by the The International Myositis
 Assessment Clinical Study Group (IMACS). The primary aim of the study is to preliminarily
 assess the safety and tolerability of etanercept in patients with DM. We hypothesize that
 etanercept 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 to 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 drugs in dermatomyositis.
Inclusion Criteria:

 Study subjects must meet the following criteria:

 1. Meet the diagnostic criteria for DM (a-c; a,b,d; or a,c,d)

 1. Subjects must have symmetric proximal greater than distal weakness

 2. Characteristic DM rash consisting of any or all of the following: heliotrope,
 shawl sign, V-sign, Gottron's sign, Gottron's papules, periungual telangiectasias

 3. Laboratory evidence of myopathy with at least one of the following: an elevated
 serum CK or aldolase level, myositis-specific antibody, electromyography (EMG)
 demonstrating myopathic features (e.g., muscle membrane instability, myopathic
 units, or early recruitment), or an abnormal skeletal muscle MRI showing diffuse
 or patchy edema within the muscles.

 4. A muscle biopsy will be optional if the patient fulfills criteria a-c. The
 subject must demonstrate symmetric proximal weakness (criteria a) for entry into
 the study. If the subject does not have a definite rash (criteria b) or
 laboratory evidence of a myopathy (criteria c), a muscle biopsy will be required.
 The muscle biopsy must demonstrate one of the following: perifascicular atrophy,
 expression of MHC 1 on perifascicular muscle fibers, MAC deposition on small
 blood vessels, tubuloreticular inclusions in endothelial cells on EM, or MXA
 expression on muscle fibers of blood vessels

 2. Newly diagnosed subjects should be able to walk independently 30 feet (cane, walkers,
 orthoses allowed). However, subjects with refractory dermatomyositis may be
 non-ambulatory.

 3. Age > 18 years

 4. Patients must not use topical skin ointments for treatment of the dermatological
 manifestations as it will interfere with skin assessment.

 5. Men and women of childbearing age must be willing to use a method of birth control.

 6. Able to give informed consent

 7. Subject or designee must have the ability to self-inject investigational product or
 have a care giver at home who can administer subcutaneous injections

 Exclusion Criteria

 The presence of any of the following excludes subject participation in the study:

 1. Presence of any one of the following medical conditions: active infection,
 uncontrolled diabetes mellitus, MI, CVA or TIA within 3 months of screening visit,
 symptomatic cardiomyopathy (congestive heart failure), symptomatic coronary artery
 disease, uncontrolled hypertension (sitting systolic BP <80 mm Hg or > 160 or
 diastolic BP > 100 mm Hg), oxygen-dependent severe pulmonary disease, systemic lupus
 erythematosus (SLE), cancer (other than basal cell skin cancer) less than 5 years
 previously, HIV or other immunosuppressing disease, positive PPD test or any history
 of mycobacterial disease, chronic hepatitis B or hepatitis C, history of multiple
 sclerosis, transverse myelitis, optic neuritis, chronic inflammatory demyelinating
 neuropathy, epilepsy, or other chronic serious medical illnesses

 2. Presence of any of the following on routine blood screening: WBC<3000, Platelets <
 100,000, hematocrit < 30%, BUN > 30 mg %, symptomatic liver disease with serum albumin
 < 3 G/DL, PT or PTT > upper range of control values

 3. Forced Vital Capacity < 50% of predicted

 4. History of non-compliance with other therapies

 5. Any prior or concurrent cyclophosphamide, or current use of any immunosuppressive
 agent besides methotrexate (e.g., azathioprine, mycophenolate, or cyclosporine)

 6. Coexistence of other neuromuscular disease that may complicate interpretation of the
 results of the study

 7. Drug or alcohol abuse within last 3 months

 8. Pregnancy or breast feeding

 9. Juvenile DM

 10. Subjects who have known hypersensitivity to Enbrel or any of its components or who is
 known to have antibodies to etanercept

 11. Use of a live vaccine 90 days prior to, or during this study.

 12. Subject is currently enrolled in another investigational device or drug trial(s), or
 subject has received other investigational agent(s) within 28 days of baseline visit.

 13. Concurrent sulfasalazine therapy