Therapeutic Advances in Myositis
Therapeutic Advances in Myositis
Advances in biological agents have led to a new era of immunotherapy in the form of monoclonal antibodies or fusion proteins that target the immune system by selectively inhibiting or depleting B cells, T cells, growth factors, transduction molecules, cytokines and costimulatory or adhesion molecules. Although many of these factors are implicated in the immunopathogenesis of myositis, their use, for the most part, should be limited to well designed prospective trials employing validated outcome measures.
Fingolimod (BAF312) is an anti-T-cell migration agent that traps T cells in the lymphoid organs, leading to a reversible 80% reduction in peripheral lymphocyte counts. This drug has an excellent safety and efficacy profile and was recently approved by the FDA for multiple sclerosis. A multicenter double blind placebo-controlled trial of Fingolimod is underway in myositis. The overexpression of Type 1 IFN-inducible genes in active myositis patients and the downregulation correlating with disease improvement suggests that an anti-IFN agent would be therapeutically beneficial in polymyositis/dermatomyositis. A phase 1 trial of anti-IFN[alpha] therapy has been initiated in dermatomyositis and polymyositis but the results are unpublished. Although biological agents are generally well tolerated, safety concerns include reactivation of latent JC virus or induction of tumors especially lymphomas.
Future Therapeutic Prospects
Advances in biological agents have led to a new era of immunotherapy in the form of monoclonal antibodies or fusion proteins that target the immune system by selectively inhibiting or depleting B cells, T cells, growth factors, transduction molecules, cytokines and costimulatory or adhesion molecules. Although many of these factors are implicated in the immunopathogenesis of myositis, their use, for the most part, should be limited to well designed prospective trials employing validated outcome measures.
Fingolimod (BAF312) is an anti-T-cell migration agent that traps T cells in the lymphoid organs, leading to a reversible 80% reduction in peripheral lymphocyte counts. This drug has an excellent safety and efficacy profile and was recently approved by the FDA for multiple sclerosis. A multicenter double blind placebo-controlled trial of Fingolimod is underway in myositis. The overexpression of Type 1 IFN-inducible genes in active myositis patients and the downregulation correlating with disease improvement suggests that an anti-IFN agent would be therapeutically beneficial in polymyositis/dermatomyositis. A phase 1 trial of anti-IFN[alpha] therapy has been initiated in dermatomyositis and polymyositis but the results are unpublished. Although biological agents are generally well tolerated, safety concerns include reactivation of latent JC virus or induction of tumors especially lymphomas.
