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The Rising Tide of Autoimmunity: Highlights of the International Autoimmunity Summit
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The International Autoimmunity Summit gathered several hundred experts who span the spectrum of autoimmune diseases, which are often referred to as immune-mediated inflammatory diseases. These included many rheumatologists, as well as dermatologists, gastroenterologists, allergists and advanced practitioners who are all engaged in the care and research of these disorders.
The meeting’s keynote speaker was Stephen I. Katz, MD, PhD, director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the NIH. He commenced by reminding attendees that the tide of autoimmune disease is increasing with estimates of 23.5 million to 50 million people afflicted with autoimmune diseases in the United States alone, depending on definitions and criteria. There are now nearly 100 different primary diseases of autoimmune origin and another 40 prominently involving autoimmune mechanisms. There is also a growing list of primary immunodeficiency diseases with dominant autoimmune/autoinflammatory phenotypes.
Accordingly, it is no wonder why such a diverse group of clinicians can successfully meet to share lessons and exchange information. In his presentation, Dr. Katz emphasized the potential impact of President Obama’s Precision Medicine Initiative. This initiative is anticipated to generate big data on upward of 1 million people. The data will include a host of information ranging from genetic information to patient-reported outcomes, which will likely yield rich insights into many diseases.
Leonard H. Calabrese
Role of Biosimilars
Several other areas appealed to the cross disciplines and generated intense interest among attendees at the meeting. The topic of biosimilars was discussed by several speakers and sparked interest and controversy. In particular, there was a rich discussion of the issue of extrapolation of indications among the subspecialists. Should a study of a biosimilar tumor necrosis factor inhibitor in psoriasis, which is positive, indicate via extrapolation that it is also effective in spondyloarthropathy for the rheumatologist or inflammatory bowel disease for the gastroenterologist?
There was an enriched discussion of immunogenicity among biologic agents across diseases shared by multiple subspecialties, which clearly can effect efficacy and toxicity. There was also a shared frustration on the legal impediments that block the advancement of biosimilars in the United States while other countries have gained some cost relief through the introduction and use of biosimilars.
Microbiome and the Immune Repertoire
There was also rich discussion on the microbiome, as presented by R. Balfour Sartor, MD, of the University of North Carolina School of Medicine. Dr. Sartor raised many provocative issues of how the microbiome clearly helps shape the immune repertoire and how manipulating the microbiome in preclinical models can influence experimental autoimmune diseases. Questions were raised about the influence beyond the bacterial microbiome, including the mycobiome and especially the microvirome, which are now entering the early stages of analysis and reporting as a result of advances in information processing.
Each bacterium is infested with its own microvirome, in the form of phages that can have resonant influences and survival. We need to remain vigilant for quality studies of this new and emerging area, despite that it is making a highly complex area even more complex.
Immune-related Adverse Events
There was discussion of new areas of autoimmunity, including the new field of immune-related adverse events (irAEs) observed in cancer patients who undergo therapy with immunologic checkpoint inhibitors. These agents, which target the “brakes” on immune activation by targeting inhibitory receptors, such as CTLA4 and PD1, have revolutionized the treatment of numerous cancers, including advanced melanoma, non-small cell lung cancer and many other tumors, especially those that have numerous mutations. A byproduct of their direct mechanism of action — which disinhibits T-cell activation — is a growing spectrum of autoimmune AEs involving the skin, bowel, liver, endocrine organs and increasingly the musculoskeletal system.
My impression from the discussion at the International Autoimmunity Summit was that few clinicians are familiar with these AEs and lack the confidence to recognize and manage these new entities. This is problematic given the increasing use of these agents in the community practice of oncology. I see two or three consultations per week at the Cleveland Clinic from my oncology colleagues. We are working with subspecialists across numerous specialties to provide multidisciplinary care for patients with numerous irAEs. Immune-related adverse events are a new field, and we have much to learn and need to educate ourselves now.
Thanks for reading this issue of Healio Rheumatology. Please send me your comments by email at calabrl@ccf.org or on Twitter @LCalabreseDO.
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- Leonard H. Calabrese, DO, is the Chief Medical Editor, Healio Rheumatology, and Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic.
Disclosure: Calabrese reports he is a consultant for Genentech, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Jansen and AbbVie; and is on the speakers bureau for Genentech, Abbvie and Bristol-Myers Squibb and Crescendo Bioscience.