Expert panelists share strategies and considerations for selecting optimal treatment pathways for patients with lupus nephritis.
Jorge Larranaga, MD: It’s nice to have 2 new data sets, which we haven’t had for at least 40 years, with respect to the treatment of these patients. We recognize that MMF [mycophenolate mofetil] took a role from the data from [the University of] Miami, and Dr [Gabriel] Contreras and Dr [Gerald] Appel. It was found to be noninferior to Cytoxan therapy, which is the original therapy from the 1980s that was approved by the NIH [National Institutes of Health]. The complications of Cytoxan therapy led to significant problems.
Around 2009, MMF took the role as the mainstay of adjunct therapy along with steroids. But as far as steroid therapy in combination with MMF or other types of regimens, we’ve known data from 2016 or 2017 that high-dose systemic steroids lead to significant end-organ complications. In particular, about 74% of new end-organ target damage occurs with steroid therapies greater than 7.5 mg per day. These data aren’t new. They’ve been out for a while. We’ve just been implementing it with the new data that have been set forward.
We recognize that steroid therapy is sometimes needed as induction therapy, but long-term usage of these drugs has led to the complications we recognize: not just as cataracts or glaucoma but also sodium retention, hypertension accelerations, and endovascular acceleration of atherosclerosis, leading to mortality of these patients with steroids. Therefore, we’re glad to see that new conventional therapies and studies have shown that we’re able to treat these patients with these new regimens but with minimal steroids in the long term. We now have other options. For T-cell or B-cell suppression, both studies are quite intriguing and have a role in the treatment of these patients, depending on your interpretation and how your outcomes are. We’re glad to have belimumab as well as MMF and voclosporin in the new regimen for our patients going forward. In the Spiriva trial, only 8.3% of patients had a complete remission, although they had different sets of guidelines. But we’re able to accomplish far better outcomes in these patients with these new types of B-cell and T-cell suppression drugs.
Alvin Wells, MD, PhD: When we diagnose a patient with lupus nephritis, it can be a little overwhelming [for them]. Think about a 32-year-old who recently married, had a couple of kids, and is being hit in the face with this diagnosis. It can be a little overwhelming. It’s even more overwhelming when we talk about medications. They hear some of the adverse effects of these drugs, and they say, “These adverse effects sound worse than my disease.” I tell them, “If we don’t control your disease and get you under control as quickly as possible, we’re going to see this disease progress.” We think about the structure inside the kidney called the nephron. I like what some of my nephrology colleagues say: “For patients with lupus nephritis, time is nephrons.” I should act very quickly to get the disease under control.
When a patient has proteinuria in their urine at baseline, we want to see a 25% decrease at 3 months and a 50% decrease at 6 months. That’s the target. If you aren’t getting there by 6 months, you need to adjust your treatment. In my practice, we start several agents up front to get patients under control. As they get better, we start pulling away drugs. The No. 1 drug we want to decrease and stop if possible is corticosteroids.
The treatment landscape is changing, but we have more long-term data supported by randomized controlled clinical trials, so the guesswork is no longer needed. You don’t have to worry about whether a drug is going to work while using older drugs that we thought worked from transplant literature and other data. Those days are gone. We now have a group of drugs that worked in clinical trials to get these patients as close as possible to control of their disease.
Transcript edited for clarity.