The Great Debate: Belimumab vs. Voclosporin in Lupus Nephritis

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ACR Convergence 2021—The Great Debate at the meeting sparked a thoughtful discussion on the future of lupus nephritis treatment strategies, with experts saying clinicians should be open to new ways of approaching patient care.

In the past year, approvals of the monoclonal antibody belimumab and the calcineurin inhibitor voclosporin for use in lupus nephritis (when combined with standard therapy) have given physicians new treatment possibilities, but they are now faced with the question of which regimen to use.^1,2

Michelle Petri, MD, MPH, professor of medicine at Johns Hopkins University, Baltimore, and director of the Hopkins Lupus Cohort, underscored belimumab’s “clean” safety profile and beneficial effects on  glomerular filtration rate (GFR). She also said clinicians should be comfortable being more aggressive in their approach.

Dr. Petri

“You need to feel comfortable using both of these new treatments,” she said. “It’s time to change our paradigm. If, at the time of biopsy, it is a bad biopsy with lots of bad prognostic markers, I don’t think we should be using mycophenolate (MMF) alone. I think we should be very comfortable starting either a calcineurin inhibitor or belimumab.”

Dr. Petri and Brad Rovin, MD, a nephrologist and professor of medicine at Ohio State University, Columbus, who reviewed voclosporin’s benefits, delved into the details of both treatments. They highlighted the following five points:

1. Response Rates

In the phase 3 trial for belimumab, those in the treatment group, who received standard care plus belimumab, had a one-year complete renal response (i.e., a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m², and no use of rescue therapy) rate (CRR) of 32.2%, compared with 26.9% for the placebo group, although Dr. Petri said the differences were better just before and after the 52-week landmark.¹ At two years, belimumab’s CRR was 30%, compared with 19.7% for placebo. In a voclosporin trial, the CRR for the drug was 41%, compared with 23% for placebo.² There was no two-year randomized clinical trial for voclosporin.

2. GFR Protection

The GFR was well protected by belimumab, which Dr. Petri suggested was one of the most important findings in the trial. From three to four months after treatment, the GFR was considerably better in patients treated with belimumab than in patients who received only standard care, she said.