Drs Wells and Larranaga discuss unmet needs in the treatment landscape for patients with lupus nephritis.
Alvin Wells, MD, PhD: When we think about lupus nephritis, we haven’t found the holy grail. We always ask, what are some of the unmet needs? As a rheumatologist, if I had a crystal ball or a magic wand, what would I want? First, I want the patients to come in. Can I predict who might go on to get lupus nephritis? We have other studies that show if a patient has a family history of rheumatoid arthritis and we do a blood test on them, we can show the blood test being abnormal 3 to 5 years before they get clinical signs of rheumatoid arthritis. So can we intervene in that patient earlier? The caveat is that I want to put them on some of these drugs that might potentially have adverse effects.
It’s the same as we talk about with breast cancer. When a young lady under the age of 50 years has breast cancer or ovarian cancer in the family, do they want to get the genetic markers that help them with the question, “Do I need to maybe have surgery or do some other things and more routine monitoring to make sure I don’t have breast cancer or ovarian cancer early on?” Those are the same goals I want for lupus nephritis. I want a tool. If you have an aunt, mother, or sister with lupus and lupus nephritis, I want to [test for] this marker on you. If it tests positive, I might want to see if I can see you every 3 to 6 months to make sure you don’t develop any disease. That’s one thing.
Once we make the diagnosis of lupus nephritis, what’s the best way I can measure that and monitor the disease response? We know we need a kidney biopsy to see how it looks under the microscope at baseline, but then we’re relying on protein in the urine, proteinuria, to follow that patient’s disease. The proteinuria goes up when the disease flares, and it goes down as the disease is under control. It doesn’t always correlate with patients with lupus nephritis, so can I have another way of measuring that disease activity, what we call a biomarker? An analogy that I use is that in somebody with prostate cancer, the PSA [prostate-specific antigen] level goes up when a man’s prostate cancer comes back, and it goes down when it’s under control. I need something similar to tell me the same thing in lupus nephritis. Can I have a predictive marker? Can I have a biomarker?
The third thing is of all of the different treatments that are out there, can I say a patient is going to respond to one drug vs another? What’s the chance they might respond to belimumab or voclosporin? Those are the 3 things that I call the holy grail. They’re unmet needs. As a rheumatologist, I wish I had those. Then maybe the future is bright in treating patients with lupus nephritis.
Jorge Larranaga, MD: Unmet needs that remain for the management of lupus nephritis include research. We’ve known about lupus nephritis since the 1980s. Patients were dying and entering dialysis left and right, and the NIH [National Institutes of Health] came up with the Cytoxan era. Subsequently, it took us from the 1980s to roughly 2012 to have MMF [mycophenolate mofetil] being introduced to the world of steroids and lupus nephritis management. In 2020, we had the addition of Benlysta, and in 2021, we had the addition of voclosporin.
We now have more research, and physicians are hungry to obtain information about these data. Because although the patient population in the world, and even in the United States it’s roughly about 300,000 patients, we recognized that when we reached these patients in our office or hospital settings, we had very little to provide to them. The status quo wasn’t enough to treat these patients. Research and further guidance in the future is much needed, and we shouldn’t stop just because we [gained] 2 drugs in 2020 and 2021.
In addition to this, as I travel across the country lecturing about lupus nephritis or other entities, I find there’s a significant lack of knowledge among medical personnel in addition to the community. Sometimes our patients are our best advisory to the community when it comes to education about new medicines or the significance and prognosis of a disease state. Therefore, as physicians, we need to do more to educate our extenders, our patients, and ourselves so that we’re able to tackle the complexity of this disease itself.
We also need research. There are a lot of disputes about when to use Benlysta or voclosporin. Can we use dual B-cell suppression and T-cell suppression in these patients? Do we use one drug over the other in the acute setting and let the other help us out in maintaining and decreasing relapses? There are pros and cons to these questions, and all these questions haven’t been answered.
As I meet more colleagues across the country, we’re trying to create anecdotal data until pharmaceutical companies get together and come up with a much-needed head-to-head or combination regimen as needed. We’re trying to get a feel for how these new drugs can work together, independently, or one after the other, depending on the patient’s situation. Recognizing that lupus nephritis is such a complex disease—it could be subtle, or it could be very aggressive very rapidly—is there an urgency? There’s an urgency, and it should be treated on a stat basis, just like cardiology treats angina and myocardial infarction. We shouldn’t fall asleep trying to get the diagnosis of these patients or provide them with proper therapy.
My final note is that the older I get and the more I deal with these complex patients, [the more] I believe in the poly MOA [mechanism of action] approach. In other words, the mechanism of action of different types of agents, not just the backbones of salt restrictions, supportive care, and blood pressure management, but perhaps the combinations of SGLT2 inhibitors, mineralocorticoid antagonists, Benlysta, B cells, voclosporin, RAS blockade, vitamin D, vitamin C, antioxidants, and other medications that can be used to aggressively treat these patients from day 1. I wouldn’t want to give the message to our nephrology and other colleagues that we should avoid these drugs as a rescue regimen, but perhaps [we should] be more proactive and aggressive from the beginning with the poly MOA approach toward these patients.
Transcript edited for clarity.