A Pilot Study of Etanercept in Dermatomyositis
Condition: Dermatomyositis
MeSH terms: Dermatomyositis
Intervention: Etanercept; Placebo
Intervention description: Etanercept 50 mg will be injected subcutaneously once per week for 52 weeks; Placebo, contained in 50mg syringes, will be injected subcutaneously once per week for 52 weeks.
Intervention MeSH terms: Etanercept
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: dermatomyositis; etanercept; tumor necrosis factor alpha

Summary:

      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.
    

Eligibility criteria:

        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