Physicians have new treatment options for patients with lupus nephritis. Investigators at The Ohio State University Wexner Medical Center helped lead clinical trials that resulted in approval of two new drugs—the first drugs ever approved for lupus nephritis by the Food and Drug Administration.
“Other than steroids, there had been no drugs approved specifically for lupus nephritis—ever,” says Brad Rovin, MD, director of the Division of Nephrology and medical director of the Center for Clinical Research Management at the Ohio State Wexner Medical Center. “This is a renaissance for lupus nephritis trials, because a number of other drug studies have been unsuccessful.
“The fact that the lupus community was able to design, conduct and achieve successful outcomes in two clinical trials is of paramount importance to further interest in the development of novel therapies for lupus nephritis. This has boosted the intellectual morale of lupus investigators.”
Lupus nephritis occurs in patients who have systemic lupus erythematosus, an autoimmune disease. Autoantibodies deposit in the kidneys, causing inflammation, kidney injury, a loss of protein and blood in the urine, and sometimes kidney failure.
“This is the most common severe manifestation of how lupus can affect the body,” Dr. Rovin explains. “About 40% to 50% of patients with systemic lupus will develop lupus nephritis.”
In December 2020, belimumab (Benlysta), which was previously approved for the treatment of systemic lupus erythematosus, was approved for lupus nephritis. In January 2021, voclosporin (Lupkynis), a calcineurin inhibitor, was approved as the first oral drug for lupus nephritis.
For both trials, Dr. Rovin and his colleagues at the Ohio State Wexner Medical Center collaborated with investigators at multiple centers around the country and around the world.
How the new lupus nephritis drugs work
Before the approval of belimumab and voclosporin, doctors relied on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent to manage their patients’ lupus nephritis.
However, patients often experienced side effects with the steroids in this standard of care, and many progressed to end-stage kidney disease at a rate that doctors considered unacceptably high. The patients' overall health and quality of life often suffered, too, during treatment.
One of the new medications for lupus nephritis, belimumab, is not a steroid; it’s a biologic therapy given by injection, in conjunction with a patient’s other lupus medications.
Basically, Dr. Rovin says, it works by decreasing B-cells and preventing the production of autoantibodies that attack healthy tissues and lead to kidney disease and kidney failure.
The other new medication, voclosporin, is an oral therapy used in combination with background immunosuppression. It acts on T-cells, another cell type of the immune system, and inhibits their function to reduce kidney injury.
“Voclosporin also tends to help the podocyte, a cell that covers the filtration unit of the kidney and is damaged in lupus nephritis. So it may act on two levels,” Dr. Rovin says.
Significant benefits and effectiveness of new lupus nephritis treatments
During their respective clinical trials, researchers added belimumab or voclosporin to the patients' background treatment. The addition of the drug, in each clinical trial, increased the kidney response rate significantly, without added side effects.
“When you add these medications to existing medicines being used by patients with lupus nephritis, it improves their kidney response rate after one year and after two years. This means we saw a stabilization or improvement of their kidney function and a reduction in the amount of protein in their urine—which we use as a marker for disease activity—to prespecified low levels,” Dr. Rovin says.
The goal of lupus nephritis treatment is to preserve kidney function and prevent or delay the need for dialysis or transplantation, and, Dr. Rovin says, these new medications improved kidney remissions at one or two years, which is critical for good long-term kidney outcomes.
“This was done without additional treatment-related toxicity—a key goal to improve the quality of life for our patients,” Dr. Rovin explains.
Field open for innovative study, precision medicine, personalized therapies
With the approval of belimumab and voclosporin, the field is wide open for further innovative investigation of more novel therapies for lupus nephritis – including the use of precision medicine and personalized treatments.
Dr. Rovin and his colleagues at the Ohio State Wexner Medical Center believe that each patient is a unique individual. Therefore, a single treatment that works for some patients may not be right for others.
“By having approved drugs to choose from, the next step is to ask, ‘How can we mix and match these drugs, study them in patients, and find the correct combination for an individual as opposed to the group?’” Dr. Rovin says. “Is it possible that a regimen with steroids could be eliminated? Is it possible to put combinations of the new drugs together to get something even better with even fewer side effects?
“There are so many possibilities now. And that’s why this is a renaissance.”
Gratitude for patients and families
Dr. Rovin is mindful that these new medications for lupus nephritis wouldn’t be possible without patients who are willing to participate in clinical trials.
“As a community of physician scientists, we appreciate the patients and families who participate in these studies. Since they’re placebo-controlled trials, the patients may or may not get the actual drug, and they realize that. They participate with the altruistic idea of helping people down the road, if not themselves. This is the way we’re going to solve this disease.”