Clinical Trial: Infliximab (Remicade ) to Treat Dermatomyositis and Polymyositis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial of Infliximab in Patients With Dermatomyositis and Polymyositis

Brief Summary:

This study will examine whether infliximab (Remicade ) 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

Detailed Summary: 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 weeks 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 were 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.
Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Current Primary Outcome: Muscle strength [ Time Frame: 16 weeks ]

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: April 11, 2002
Date Started: April 5, 2002
Date Completion:
Last Updated: April 20, 2017
Last Verified: March 20, 2017