Therapy of autoinflammatory syndromes

Abstract

The therapy of autoinflammatory syndromes is an excellent example of the power of translational research. Recent advances in our understanding of the molecular and immunologic basis of this newly identified classification of disease have allowed for the application of novel, effective, targeted treatments with life-changing effects on patients. Although colchicine and TNF-α inhibitors are important therapies for specific autoinflammatory syndromes, the novel IL-1-targeted drugs are particularly effective for many of these diseases. Recently, the pharmaceutical industry has adopted a strategy of confirming the efficacy of new targeted drugs in often-ignored patients with orphan diseases, and US Food and Drug Administration policies have allowed for accelerated approval of these drugs, creating a win-win situation for patients and industry. This article reviews the general approach to the therapy of autoinflammatory diseases, focusing on current approved therapies and novel approaches that might be used in the future. Keywords Autoinflammatory; IL-1; inflammasomeThe traditional clinical classification of immune-mediated diseases, including allergy, immunodeficiency, and autoimmunity, is based on differences in immunologic mechanisms and clinical symptomatology and has defined the medical specialties caring for patients with immune-mediated illnesses for more than 60 years. However, in the last 10 years, a new category of immunologic disease, known as autoinflammatory diseases, has been created to account for disorders that did not fit well into the classical disease groups. 1 Although patients with these disorders can present with classic rheumatologic symptoms, including inflammation involving the joints, skin, muscles, and eyes, the underlying inflammatory mechanisms do not involve autoantibodies or antigen-specific T cells. 2 Some patients also display episodic or precipitated symptoms, including urticaria and conjunctivitis, similar to those seen in allergic patients, but there is no evidence of IgE-mediated inflammation. Recurrent fever is a common feature of both autoinflammatory disorders and infections caused by immune deficiency. However, insufficient immune response to pathogens is not an immunologic characteristic of autoinflammatory diseases.Reprint requests: Hal M. Hoffman, MD, University of California at San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093-0635. hahoffman@ucsd.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe autoinflammatory disorders are characterized by dysregulation of innate immunity, the arm of the immune system considered to be more primitive and less specific. Instead of lymphocyte or antibody responses to specific antigens based on a memory of prior exposure, innate immune cells, such as macrophages and dendritic cells, sense conserved pathogenassociated molecular patterns. The primary effectors of the innate immune response are myeloid cells, such as neutrophils and monocytes, and proinflammatory cytokines...