Infliximab (Remicade(Registered Trademark)) to Treat Dermatomyositis and Polymyositis
This study will examine whether infliximab (Remicade(Registered Trademark)) is safe and effective for the treatment of dermatomyositis and polymyositis. Infliximab blocks the effect of a protein called tumor necrosis factor (TNF), which is associated with harmful inflammation in many diseases.
Patients 18 years of age and older with active dermatomyositis or polymyositis that does not respond adequately to treatment with methotrexate and corticosteroids may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, pulmonary function test, skin test for tuberculosis, HIV test, electromyography (described below), manual muscle testing, and functional assessments. Magnetic resonance imaging (described below) will be done to assess the degree and location of inflammation in the involved limbs. An electrocardiogram and echocardiogram will be done if recent ones are not available. Patients who qualify for the study will be asked to undergo two muscle biopsies (surgical removal and analysis of small pieces of muscle tissue), one before initiation of treatment and another on the 16th week .
Participants will be randomly assigned to receive either 3 mg/kg body weight of infliximab or a placebo (inactive substance) by infusion through a vein over 2 hours. The infusions will be given at the beginning of the treatment period (week 0) and at weeks 2, 6 and 14. At week 16, strength will be assessed by manual muscle testing. Patients who improved with treatment will continue with the same infusion dose on weeks 18, 22, 30, and 38. Those who do not improve will be assigned by random allocation to receive either 5 mg/kg body weight or 10/mg/kg body weight of infliximab on weeks 18, 22, 30 and 38. Those who did not improve who were previously on the placebo infusion will receive an extra dose of either 5 mg/kg or 10 mg/kg body weight of infliximab on week 16, while those patients who were previously on 3 mg/kg body weight of infliximab who failed to meet the improvement criteria will receive an infusion containing no medication on week 16. Patients will be admitted to the hospital for infusions at weeks 0, 14 and 38; the rest will be given on an outpatient basis. After the 38th week, all infusions will be stopped and patients will be assessed on the 40th week.
Participants will undergo some or all of the following tests and evaluations during treatment:
- Blood tests every week to look for antibodies seen with muscle inflammation. Some of the blood samples will be stored for later testing, including genetic studies to find genetic differences related to inflammation.
- Skin test for tuberculosis
- Chest x-rays at the beginning of the study (if a recent one is not available) and again at weeks 16 and 40 to look for active infection, detect signs of past exposure or infection with diseases such as tuberculosis, and assess the presence of lung disease that might be related to the myositis.
- MRI (usually of the legs) at the beginning of the study and again at weeks 16 and 40 to measure disease activity and extent of muscle involvement. This will also give an idea of the response to treatment. This test uses a magnetic field and radio waves to produce images of body tissues. During the procedure the patient lies on a bed surrounded by a metal cylinder (the scanner).
- Muscle biopsy at the beginning of the study to diagnose muscle inflammation and again at week 16 to evaluate the response to treatment.
- Electromyography if the patient has not had an EMG previously. For this test, small needles are inserted into the muscle to assess the electrical activity of the muscle
- HIV test
Patients whose disease worsen with treatment or who develop serious drug-related side effects will be taken off the study and referred back to their primary care physician for further therapy. Patients who improve will be referred back to their primary physician at the end of the study for possible continued treatment. Participants will be asked to return for follow-up visits every 6 weeks for a total of 30 weeks to monitor long-term effects of the drug
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
- Muscle strength [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||April 2002|
|Study Completion Date:||May 2010|
|Primary Completion Date:||July 2007 (Final data collection date for primary outcome measure)|
Tumor necrosis factor (TNF), a cytokine that has been implicated in the pathogenesis of many diseases including inflammatory disorders, has been found to be elevated in the muscles of patients with dermatomyositis (DM) and polymyositis (PM). A subset of patients with DM and PM do not respond readily to conventional therapy. Therefore, a controlled trial using infliximab, a chimeric IgG(1) kappa monoclonal antibody against TNF, may provide a therapeutic option and advance understanding in the pathogenesis of these diseases. This study is designed to determine the safety and efficacy of infliximab in patients with DM and PM. We plan to enroll a maximum of 28 patients randomized at 1:1 ratio into 2 groups, placebo vs. infliximab at 5 mg/kg body weight. In the first phase of the study the placebo and infliximab infusions will be given at week 0, 2, 6 and 14. Primary outcome assessment will be done at week 16. Those who respond according to the criteria set for improvement in MMT will be given the option to remain on the same infusion (i.e. placebo or infliximab at 5 mg/kg body weight) at week 22, 30 and 38. Placebo non-responders will be given infliximab at 5 mg/kg body weight in an open label fashion at weeks 16, 18, 22, 30 and 38. Patients who are initially on 5 mg/kg body weight of infliximab who failed to respond based on the criteria set will be placed on infliximab at 7.5 mg/kg body weight in an open label fashion on weeks 22, 30 and 38. Pharmacokinetic modeling will be done in both phases of the study. A muscle biopsy will be done before treatment and again at 16 weeks of treatment. Microarray gene expression profiling of the muscle biopsy specimens will be done before treatment and again at 16 weeks. Clinical, functional and serological evaluations will be performed in every visit to assess other responses to treatment. Patients will be followed for 30 weeks after study termination to evaluate the long-term effects of the drug.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Adam I Schiffenbauer, M.D.||National Institute of Environmental Health Sciences (NIEHS)|