Clinical Trials Logo

Clinical Trial Summary

The purpose of this multi-center pilot study is to determine if the drug tocilizumab (Actemra) is effective in the treatment of patients with refractory adult polymyositis (PM) and dermatomyositis (DM).


Clinical Trial Description

Although there are several studies supporting the efficacy of tocilizumab (TCZ) in Rheumatoid Arthritis (RA) and systemic onset juvenile idiopathic arthritis, it's use in other autoimmune disorders has also been propose. A consensus statement on blocking the effects of IL-6 in RA and other autoimmune conditions has been recently published. IL-6 is involved in the growth and differentiation of many inflammatory cells. In addition to its initial role in triggering B-cell stimulating factor, it also induces T cell growth and differentiation and plays a critical role in both adaptive and innate immune responses. IL-6, produced by many cells including T cells, B cells, monocytes and endothelial cells, binds to its receptor (IL-6R) and subsequently triggers several intracellular pathways leading to the release of inflammatory mediators and stimulation of the immune system. Inhibition of IL-6 has been studied in phase II and III clinical trials of RA. It has led to a decrease in acute phase reactants and other indicators of chronic inflammation. IL-6 is also a potential therapeutic target in systemic sclerosis, and since IL-6 induces differentiation of B cells into antibody forming cells and contributes to T cells transforming into effector cells, its use in Systemic Lupus erythematosus (SLE) has also been suggested. The use of TCZ in myositis proposed in this protocol is supported by the aforementioned rationale and its efficacy in other rheumatologic disorders. Patients with refractory polymyositis (PM) were treated with tocilizumab and responded favorably. In dermatomyositis, tissue inflammation implicates soluble cytokine networks contributing to disease pathogenesis. Work on a mouse model of myositis noted IL-6 as a mediator of muscle inflammation. Other investigators studying peripheral blood samples and clinical data on both adult and juvenile dermatomyositis (DM) noted that serum levels of IL-6 were significantly correlated with disease activity. In this same study, correlations between serum IL-6 levels and both the type I interferon gene and chemokine signatures were also identified in DM. These authors suggest that the coordinated dysregulation of IL-6 production and Type I interferon signaling implicates these pathways as contributing to disease pathogenesis in DM. In a mouse model of PM, C protein-induced myositis (CIM), the pathology reportedly mimics that seen in human PM. Mice were treated with anti-IL-6 receptor monoclonal antibodies or control antibodies and muscle tissue was histologically and immunohistochemically analyzed. CIM was ameliorated in this mouse model implicating IL-6 in the development of myositis. These results not only identified this model as useful to understanding PM but they suggest that IL-6 blockade be considered as a new therapeutic approach in the treatment of myositis. Thus, the collective findings described above provide evidence for the involvement of IL-6 in the pathogenesis of both adult PM and DM as well as supporting its role from animal models and human studies. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02043548
Study type Interventional
Source University of Pittsburgh
Contact
Status Completed
Phase Phase 2
Start date October 1, 2014
Completion date July 31, 2019

See also
  Status Clinical Trial Phase
Recruiting NCT05833711 - Study Evaluating Efficacy and Safety of Froniglutide (PF1801) in Patients With Idiopathic Inflammatory Myopathy Phase 2
Not yet recruiting NCT06284954 - A Study to Evaluate Safety and Efficacy of Empasiprubart in Adults With Dermatomyositis Phase 2
Completed NCT01906372 - Acthar in Treatment of Refractory Dermatomyositis and Polymyositis Phase 2
Completed NCT01813617 - Outcome in Patients With Recent Onset Polymyositis and Dermatomyositis N/A
Completed NCT01165008 - Anakinra in Myositis Phase 2/Phase 3
Completed NCT00004357 - Absorption of Corticosteroids in Children With Juvenile Dermatomyositis Phase 2
Recruiting NCT05832034 - Add-on Intravenous Immunoglobulins in Early Myositis Phase 2
Recruiting NCT05979441 - A Study to Assess the Long-term Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Active Idiopathic Inflammatory Myopathy Phase 3
Not yet recruiting NCT05027152 - Muscle Function and Effects of Repetitive Task Training in Patients With Inflammatory Myopaties N/A
Active, not recruiting NCT04723303 - Phase 1 Study of ULSC in Patients With Polymyositis (PM) and Dermatomyositis (DM) Early Phase 1
Completed NCT03267277 - Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis Phase 2/Phase 3
Recruiting NCT05437263 - A Study to Investigate the Efficacy and Safety of Brepocitinib in Adults With Dermatomyositis Phase 3
Active, not recruiting NCT04044690 - A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of IgPro20 in Adults With Dermatomyositis (DM) Phase 3
Recruiting NCT05523167 - A Study to Investigate the Efficacy and Safety of Efgartigimod PH20 SC in Adult Participants With Active Idiopathic Inflammatory Myopathy. Phase 2/Phase 3
Not yet recruiting NCT06004817 - Evaluation of Severity in Juvenile and Adult-onset Dermatomyositis
Recruiting NCT03324152 - Effects of High-intensity Interval Training (HIIT) in Recent Onset Polymyositis and Dermatomyositis N/A
Completed NCT03414086 - Predictor of Clinical Response to Acthar in Myositis
Completed NCT04628936 - Open-label Extension to the Phase 2 Crossover Study (PRESIDIO) Evaluating KZR-616 in Patients With PM and DM. Phase 2
Recruiting NCT03293615 - Exercise Capacity of Patients With Dermatomyosis N/A
Recruiting NCT06462768 - Neutrophil Extracellular Traps in Different Forms of Systemic Sclerosis