There is increasing, and necessary, attention on an open secret: the epidemic of steroid-toxicity. We sat down with Dr. John Stone, Professor of Medicine at Harvard Medical School, rheumatologist, the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, and Chair of the Scientific Advisory Board at Steritas. To learn more about the impact of steroid exposure on patients and healthcare systems, we posed a series of questions including about The Great TaperTM initiative, a public health movement to alter steroid-prescribing patterns. After graduating from Harvard Medical School, Dr. Stone completed his internal medicine training at Johns Hopkins University School of Medicine and a rheumatology fellowship at the University of California-San Francisco. Before being recruited to Mass General in Boston, he co-founded and directed the Vasculitis Center of Excellence at Johns Hopkins in Baltimore. His expertise is in vasculitis, a group of inflammatory diseases that target blood vessels. Dr. Stone is also a thought leader on a newly-described multi-organ condition known as IgG4-related disease (IgG4-RD). He has led pivotal trials in ANCA-associated vasculitis, giant cell arteritis, and IgG4-RD, all leading to the worldwide approval of new treatments for those diseases.
Since 2015, drawing on 25 years of experience with glucocorticoid treatments for his own patients, Dr. Stone has focused on the measurement and prevention of glucocorticoid toxicity to help transition the treatment of patients with inflammatory diseases into an era of safe, effective, steroid-toxicity sparing medications. Recognising the need to research, monitor, and reduce the use of steroids in patients and populations, he convened an international group of experts to lay the foundations for development of the Glucocorticoid Toxicity Index (GTI), now part of the STOX Suite, a collection of validated clinical outcome assessment (COA) to measure steroid-toxicity.
Q. How are steroids used in the treatment of autoimmune and autoinflammatory diseases?
A. The first clinical use of steroids was in 1948 for the treatment of a young woman with rheumatoid arthritis, a medical breakthrough that earned the researchers the 1950 Nobel Prize in Medicine. Since then, steroids have been the first-line treatment for dozens of diseases caused by inflammation. Steroids are a class of medications that includes cortisone, hydrocortisone, prednisone, prednisolone, and others. Together, these medications are referred to as glucocorticoids, or corticosteroids. Glucocorticoids are useful in treating inflammatory diseases such as arthritis, asthma, Crohn’s disease, lupus, vasculitis, autoimmune blistering skin conditions, and sarcoidosis. Steroids suppress the immune system quickly and are employed in the interest of exerting fast-acting control over inflammation by
inhibiting the initial events of an inflammatory response, including reducing vasodilation and decreasing white blood cell emigration to the site of injury or inflammation. Glucocorticoid receptors are expressed throughout the body, making steroids effective against almost all immune cells, but also leading to multiple potential off-target effects.
Within 23 days of that first steroid dose administered in 1948, the first steroid toxicities were reported and thus began the first steroid taper to a lower therapeutic dose. Since then, leading experts have been looking to research, monitor, and reduce the use of steroids in patients and populations. But progress in tapering glucocorticoids has been slow, due largely to the lack of effective alternatives, consensus among clinicians on which health domains to measure and how to measure them, and the technology to make such measurement practical. Now we have the tools to quantify steroid-toxicity, we’re in a position to accelerate a shift in treatment options. This includes recent developments in our understanding of the glucocorticoid receptor itself, opening new avenues for novel steroid-sparing treatments with fewer damaging side effects.
