Recorded at the 6th McMaster International Review Course in Internal Medicine (MIRCIM).
Dr Kim Legault is an associate professor of medicine at the Faculty of Health Sciences, McMaster University, rheumatologist, and coauthor of Canadian Rheumatology Association recommendations on systemic lupus erythematosus.
If you were to name the 3 most important recent advances in the management of systemic lupus erythematosus (SLE), what would they be?
Kim Legault, MD, MSc: To me, recently, the majority of the key advances in lupus management center around the development and discovery of novel therapeutic agents. Following the success of biologic therapies in other autoimmune diseases, like the anti–tumor necrosis factor medications in rheumatoid arthritis, patients and physicians alike in the lupus community have been really hoping for similar successes and development of biologics that have efficacy in reducing disease activity in systemic lupus erythematosus. This has certainly proven challenging, as many therapies that are used in rheumatoid arthritis haven’t shown similar efficacy in the setting of lupus. However, we have been recently encouraged by some successes. Several years ago, the anti–B lymphocyte stimulator, belimumab, has been the first biologic approved in lupus. And most recently, a randomized controlled trial, published in 2020, of biologic medication called anifrolumab, which is a human monoclonal antibody against type 1 interferon receptor, [showed that anifrolumab] met its primary efficacy endpoint in its randomized controlled trial. This medication targets the type 1 interferon pathway in lupus, which has been known for many years to be a pathway that seems to be implicated in disease pathogenesis, and we’re hoping that anifrolumab shows further successes in the management of patients with lupus.
The second exciting advancement is specifically in the therapeutics that have been added to our arsenal for lupus nephritis and in terms of success in clinical studies. The first is voclosporin, which is a calcineurin inhibitor. After the 2020 phase 3 AURORA study, this demonstrated higher renal response in patients in whom voclosporin was added to standard-of-care mycophenolate. In addition, belimumab, which has been approved, as I said, for nonrenal systemic lupus erythematosus for several years, was also shown in a randomized controlled trial to have higher renal response when added on to the standard therapy for nephritis. A regulatory approval is ongoing for these indications and funding considerations will follow. We don’t know where these will be in our armamentarium, but hopefully we will have use of these agents soon.
The last advance is a methodologic one that I think is still to some degree of work in progress, but I think it’s important to highlight the work that is being done to develop valid and reliable measures of disease activity in lupus that can be used in clinical trials. The concern with many lupus clinical trials over the last decade has been the possibility that the medications are failing to help with the disease, but maybe we as researchers are not appropriately capturing improvement in disease activity, leading to false negatives in studies. And the development of new outcome measures such as a potential LFA-REAL outcome and the definition of lupus low disease activity state in recent years, I’m really hoping, will improve our ability to accurately study patients with lupus.