November 10-15

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Home // The Great Debate: Enhance lupus nephritis therapy with belimumab or voclosporin?

The Great Debate: Enhance lupus nephritis therapy with belimumab or voclosporin?

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4 minutes

The recent U.S. Food and Drug Administration (FDA) approval of two new add-on drugs — belimumab and voclosporin — has changed the treatment landscape for the management of lupus nephritis. With strong clinical trial evidence supporting the efficacy and safety of both agents, the question is which to add first to standard therapy.

Michelle Petri, MD, MPH
Michelle Petri, MD, MPH

Two expert clinicians and lupus specialists tackled this question in the annual Great Debate session, Enhancing Lupus Nephritis Therapy: Is Your Next Step Belimumab or Voclosporin? The session, which was originally presented Saturday, Nov. 6, can be viewed by registered meeting participants through March 11, 2022.

Advocating for the monoclonal antibody belimumab, Michelle Petri, MD, MPH, reviewed data from the Two-Year, Randomized Controlled Trial of Belimumab in Lupus Nephritis. She pinned much of her argument on belimumab’s strong safety profile, noting concerns about nephrotoxicity with the use of calcineurin inhibitors such as voclosporin.

“As rheumatologists, when we pick regimens for our patients, we always have to take safety into account because many of our patients are quite vulnerable,” Dr. Petri said. “With the calcineurin inhibitors, there’s the risk of acute nephrotoxicity due to vasoconstriction, which is why we have to monitor GFR and either reduce or stop the calcineurin inhibitor if there is a GFR decrease.”

The belimumab trial demonstrated GFR protection as early as three to four months that was maintained at two-year follow-up, she noted.

“This is especially important as the FDA has now accepted GFR trajectory as a surrogate for end-stage kidney disease in trials,” Dr. Petri said. “Another important take-home message about belimumab is that it’s been shown in novel analyses to prevent time-to-organ-damage progression.”

Belimumab is also superior to voclosporin relative to cardiovascular risk factors. Dr. Petri said.

“As we all know, cardiovascular disease is one of the major causes of death in our lupus patients, and we know that calcineurin inhibitors as a class can increase hypertension, diabetes, and hyperlipidemia,” she said. “In the voclosporin trial, there was no increase in diabetes or hyperlipidemia, but as expected, there was an increase in hypertension, whereas belimumab does not increase hypertension.”

Belimumab potentially has an advantage over voclosporin in terms of patient adherence as well, she said.

“Unfortunately, adherence is a big issue in our young lupus patients,” Dr. Petri said. “The reason some of our patients don’t do well with lupus nephritis is nonadherence. One advantage to belimumab, since it’s a systemic therapy, is that we will have an objective way to track adherence.”

Brad Rovin, MD
Brad Rovin, MD

Brad Rovin, MD, the Lee A. Hebert Professor of Nephrology and Division Director of Nephrology at Ohio State University Wexner Medical Center, followed with data from the AURORA 1 trial and other studies supporting the use of voclosporin, which demonstrates some important differences from legacy agents in the calcineurin inhibitor class, he said.

“While it is structurally similar to cyclosporine, for example, there’s one single carbon bond extension change, and this little modification changes how voclosporin binds to calcineurin,” Dr. Rovin explained. “This actually results in a very consistent dose response and potentially eliminates the need for therapeutic drug monitoring, which is required in solid organ transplantation when we use calcineurin inhibitors.”

This structural modification also increases the potency of voclosporin and, when added to standard therapy, results in an improved lipid and glucose metabolic profile compared to other calcineurin inhibitors, he said.

“We need much less glucocorticoid when we use this regimen, and this should translate to improved patient satisfaction and to better adherence in the short term, and hopefully less damage in the long term from glucocorticoids,” Dr. Rovin said.

Voclosporin also demonstrated rapid reduction in proteinuria, which Dr. Rovin said should translate into better preservation of GFR and may also be favorable in terms of fewer lupus nephritis flares and less accumulation of chronic kidney injury.

“The reason that the GFR declines is that glomerular perfusion is slightly decreased by the calcineurin inhibitor, and that decrease in intra-glomerular pressure also tends to result in a benefit in terms of glomerular sclerosis over the long term,” he explained. “And finally, there’s no increase in serious adverse events with voclosporin, and the drug has fewer side effects in terms of the metabolic profile than the legacy calcineurin inhibitors.”

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