title: Interferon α-targeted therapy.
abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies to various cellular components. Although many of therapies have shown great efficacy, they often associate with adverse effects. The development of safer therapies for SLE has led to recent emphasis on targeting selected pathways that can be important in the inflammatory process in SLE. The cytokine family of type I interferons (IFNs), and especially the IFNα subtypes, are implicated in pathogenesis of SLE. Genetic polymorphisms of several components of the IFN signaling pathway have been associated with an increased risk of SLE. Therefore, IFNα subtypes have been identified as a potential target for drug development in SLE. There have been developed three agents, IFNα-targeted therapy, Sifalimumab, Rontalizumab and NNC 0152-0000-0001. They are anti-IFNα monoclonal antibodies that bind to and specifically neutralizes most IFNα subtypes, preventing signaling through the type I IFN receptor. The safety and dose-proportional pharmacokinetics of those agents were demonstrated. A larger study is currently ongoing, further safety profile will be evaluated. This review provides an update on the ongoing clinical trials of anti-IFNα therapy and the promise and obstacles in the use of biologics in SLE.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine.
authors.forename: Hironari
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D006801:Humans; D016898:Interferon-alpha; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D016898:Interferon-alpha; C577244:rontalizumab; C568334:sifalimumab