“If you ask the doctor and patient what they want most of all, their unanimous answer will be, ‘not to have to use steroids.’”
Murray Urowitz MD. FRCP(C) is a rheumatologist who has spent the “last many, many years” focusing on systemic lupus erythematosus (SLE). He is a Professor at the University of Toronto Department of Medicine and received the 2019 Dean’s Lifetime Achievement Award for Global Impact in 2019 for his contributions to improving the lives of lupus patients and in the process developing several generations of physicians.
He is a named author on more than 450 medical publications and has documented that often the greatest source of damage in SLE patients is actually the treatment of lupus with glucocorticoids.
Dr Urowitz’s work has contributed to a dramatic improvement in the outcomes expected for lupus patients. Just 50 years ago, the 5-year patient survival rate for people suffering from lupus was only about 50%. Today the 20-year survival rate is approaching 90%.
During our conversation, Dr Urowitz explained how he wasn’t initially sure about his career path, but that he became enthralled by medicine during his pre-med course and then the concept of ”how our own immune system, which is supposed to protect us, actually can turn on us and cause such damage to lupus patients and affect so many different parts of the body.”
“For example, lupus patients may present with arthritis, skin disease, lung disease, heart disease, or central nervous system disease, - lupus can really direct the immune system to attack pretty much any part of the body.”
During the course of his career, he has helped collect one of the largest data sets and longitudinal studies on the disease, and in the process has transformed our understanding of how SLE presents in patients, its underlying mechanisms and how it should be treated. Dr Urowitz’s team would see patients every three to six months and collect some 400 data points as part of a standardized protocol he had developed - they now data points from 2100 patients across some 70,000 visits.
This data has enabled Dr Urowitz to describe patient outcomes and also show that if patients survive long enough they develop a whole new set of diseases.
“Sadly, it's not enough that patients are generally ill with lupus but the disease AND its treatment with steroids can cause a whole new series of illnesses like atherosclerotic heart disease - which is atypical in a similar age and sex-matched cohort in the general population. Premenopausal women just don't develop heart disease, but sadly women with lupus do.”
His research has also uncovered that even when patients with lupus seem to have their symptoms under control, they appear to also suffer some cognitive decline either due to previous active lupus disease or its therapies.
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The data set and frequent collaborations with scientists have also contributed to a better understanding of the underlying mechanistic causes of the disease, which in turn has led to a better understanding of how to treat patients.
“In the beginning when I first started my research in this area, there were very few therapies for lupus including antimalarials and corticosteroids, the latter often used in high doses and for prolonged durations. Then came the immunosuppressant drugs the atom bombs, which knocked out the immune system. All you could do was hope you were preferentially knocking out the bad things and helping the lupus. Sadly, many people suffered from more infections or more malignancies, but as we got better with manipulating that treatment, the bad effects were less marked.”
“Today, we're not limited to using an atom bomb. We're able to use a “tickling” approach where you go after just one part of the immune system, with newer biologic or small molecule therapies that target the part that's contributing to the aberrant function.”
“Many of my articles describe the side effects of corticosteroids: eye atherosclerosis or the premature heart disease is in a significant part caused by the corticosteroids because they give you high blood pressure, high cholesterol, high blood sugar - all the things that lead to heart trouble. So if women with lupus are taking glucocorticoids over a period of time, they're going to get all those bad things.”
“One other, terrible effect is that you may give glucocorticoids to treat arthritis and lupus and it's very effective, but has a terrible effect on bone. It thins the bone and actually kills parts of the bone - damaging it irreparably - and patients get a side effect called osteonecrosis.”
“What we've had to do over time is modulate use, so the first approaches were to decrease the amount of corticosteroid given and then decrease the time the corticosteroid has to be taken.”
Dr Urowtiz explains that until the development of the Glucocorticoid Toxicity Index, there was no hard objective way of measuring the decrease in steroid toxicity as the steroid doses were decreased.
“It's very important to recognize that the Glucocorticoid Toxicity Index measures those acute manifestations that are caused by steroids over a relatively short period of time and that's important to measure because all studies now want to know is: ‘were you able to take away the corticosteroids and the bad side effects.’”
“It doesn't matter whether you're in a study or whether you're a clinician looking after patients, one of your goals is to reduce the amount of cortisone, either because they don't need it anymore, or because they are starting newer therapy and that newer therapy should be giving us the ability to reduce the steroid - it's really important to be able to measure the impact of changing the dose.”
“If you ask the doctor and patient what they want most of all, their unanimous answer will be, ‘not to have to use steroids.’”
Dr Murray Urowitz is a Professor of Medicine at the University of Toronto, Senior Staff Rheumatologist at the Toronto Western Hospital, and Senior Scientist at Krembil Research Institute as well as the Clinical Director, Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network