Expert Opinion: Misreading Mortality in Lupus
“Over the years, pioneering physicians, using therapies borrowed from other diseases, have painstakingly developed treatment regimens that have helped to reduce mortality associated with lupus. Unfortunately, people suffering from certain forms of lupus, such as lupus-related kidney disease (known as lupus nephritis), cardiovascular disease and other complications, remain at a very high risk for premature death,” Raymond said in her post.
Lupus nephritis itself is currently linked with a six-fold increase in mortality and robust clinical evidence exists to show that lupus patients generally have at least a double the risk of heart disease and stroke compared to non-lupus patients.
Raymond wrote that lupus mortality is rarely heard of mostly because the deaths are usually attributed to the consequences of lupus, like kidney or heart failure. Lupus is frequently dismissed as being the primary cause of death which makes it harder to determine the true impact of the disease.
“The history of lupus drug development has been filled with challenges,” Raymond explained. “These hurdles include the way clinical trials are designed and conducted and the requirement that new medications be tested against potent therapies that patients are already taking when they enter a trial. These therapies include chemotherapies and high doses of steroids. This requirement sets a very high, almost insurmountable bar to meet in order to get new lupus drugs through the review and approval process.”
According to Raymond, the last treatment to be approved for systemic lupus erythematosus (SLE) was the monoclonal antibody Benlysta (belimumab) in 2011 after five decades of no therapeutic answers. Most therapies used by lupus patients are off-label and have not been investigated for the specific purpose of treating the disease.
Raymond also responded to media stories regarding an announcement by Aurinia Pharmaceutical Company that revealed positive top-line results for the Phase 2b clinical study of voclosporin, a potential new therapy for people with active lupus nephritis. The Phase 2b trial was the first-ever for a medication to treat active lupus nephritis that successfully reached its primary endpoint of demonstrating greater complete remission.
Raymond believes the trial results should have been regarded by the media “as a big win for this medically underserved disease”, but instead some articles focused on the number of deaths associated with it without realizing that the study included a group of already very seriously ill patients with very few options.
“The truth is people around the world are dying every day from the complications of lupus. A review of the scientific literature would have revealed that many active lupus nephritis trials had a similar number of mortalities. The history of this disease was overlooked, even diminished, when the results of a successful trial were misinterpreted,” Raymond wrote.
She suggested that accurate statistics on the incidence and prevalence of lupus, and the disease’s associated rate of mortality are needed first and foremost.
“Next, we must have a much more robust lupus research effort at the National Institutes of Health (NIH) and in the private sector to better understand the biology of the disease and establish additional targets for drug development,” Raymond wrote. “Moreover, the FDA, working with key lupus experts, must figure out better ways to design clinical trials so they can be shorter, smaller and less expensive. Additionally, the public and our policy makers must understand that lupus is a devastating disease that can have life-threatening and life-altering consequences.”