Alvin Wells, MD, PhD, provides an overview of the lupus nephritis treatment landscape.
Alvin Wells, MD, PhD: There are a lot of drugs being used to treat patients with lupus nephritis. For example, going back to my analogy about what lupus is, these angry cells are turning, and they spill out of the bloodstream and get into the kidneys, causing lupus nephritis. I want to give drugs that dampen the immune system. I use another analogy that [being] young and healthy balance out the scale, but with lupus nephritis, the scale is tilted on the negative side. Those angry cells are attacking the kidneys. I want to see if I can get it back to as balanced as I can. I don’t want to go too low because we’re going to see some adverse effects. That’s why we talk about our drugs as more like immunosuppressor drugs.
One of the hallmark drugs we use are corticosteroids—mostly prednisone or methylprednisolone. Those drugs are great, but it’s a double-edged sword. They work very quickly. They can get some patients into significant control. But we can’t keep patients on them long term, because with long-term corticosteroids, I’ve got to get back to that balance. I don’t want a young, 30-year-old woman to get cataracts or diabetes or have osteoporosis of her bones. Those are features that we worry and think about regarding what’s good and the bad for some of these treatments.
In addition to corticosteroids, we use other immunosuppressive drugs. Mycophenolate mofetil is one of the hallmarks, along with cyclophosphamide. All of those drugs were borrowed from our oncology counterparts to dampen the immune system. Those are potent drugs, but we don’t want to give too much and turn the immune system too low, because then we see increased risk of certain types of infections and of cancers.
For example, cyclophosphamide is used, and a study is coming out from the NIH [National Institutes of Health] and Europe showing that it works for patients with lupus nephritis, but even after 1 dose of that medication, I have to tell the patient, “I need to monitor you on a regular basis to make sure you don’t go on to get bladder cancer coming from the medication.” Mycophenolate is a great drug. I usually prefer it at my practice. It doesn’t have all the other adverse effects, but it’s still an immunosuppressive drug. I want to make sure patients aren’t going to get bowel infections, pneumonia, and other types of illnesses that are triggered by that.
Then we talk about a class of drugs called the calcineurin inhibitors. These drugs work in a number of ways. We’re learning that some of these newer agents are targeting the immune cells, such as the T cells, and they’re stabilizing the part of the cells that anchor the kidneys together, making that dam intact: the podocytes. The landscape has changed. The days of treating people willy-nilly are gone. We have targets in mind. I talked earlier about the goals we set with our patients with lupus. They want to reduce their pain, fatigue, and swelling of the legs. I say, “I want to get the protein in your urine down by 50% in 6 months.” There’s a ratio in which we look at the protein and the urine vs the creatinine. I want to make sure that number goes down to 0.5 mg/dL or less.
There are certain features and targets that we use. With the corticosteroids that we use as a bridge therapy, the No. 1 goal is to get the corticosteroid dose down to less than 7.5 mg. When I was doing my fellowship at Duke University, we talked about 10 or 15 mg of prednisone. That was a low dose. We’ve learned so much more [since then], including that 7.5 mg or more can cause more harm than good. Now I want to get my patients off if possible, or to a target of 2.5 or 5 mg. That means that the landscape in treating patients with lupus nephritis has changed, which is exciting for our patients who have active disease.
When you think about our different treatment options for lupus nephritis, I want drugs that are FDA approved. When you think about drugs that aren’t FDA approved, they’re experimental, and patients don’t come to my practice wanting to experiment . They want to get the best treatment options based on evidence-based medicine, and that’s what we do. I tell my colleagues, “That’s what we all should be doing.” Let’s start with evidence-based medicine to get these patients under control.
[We don’t want to] use drugs that we think have worked. We want to say, “We go to things that have been shown in randomized controlled clinical trials, and these are the ones that the FDA mandates.” This leads to getting data in the peer-reviewed journals. The rheumatology and nephrology journals are all out there to vet those [drugs]. There aren’t many FDA-approved drugs. We have corticosteroids and calcineurin inhibitors, such as voclosporin. These were vetted in clinical trials, which showed that when patients have been on the drug for 1 or 2 years—we now have long-term data—we can decrease the protein in the urine, preserve the glomerular filtration rate, and do that in the setting of low-dose corticosteroids. Many drugs are out there, and some of my colleagues are using them, but they aren’t FDA approved. My patients are demanding me to give the best medication supported by the best evidence.
Transript edited for clarity.