Anca Askanase, MD, professor of medicine at Columbia University School of Medicine, New York, presented the final segment on therapeutic options for refractory lupus nephritis. Per the ACR Guideline, for patients with SLE who have proteinuria of >0.5g (or a UPCR >0.5g/g) and/or impaired kidney function not otherwise explained, they conditionally recommend performing a percutaneous kidney biopsy.
For patients with active, newly diagnosed or flare of Class III/IV (with or without concomitant Class V) lupus nephritis, the guideline conditionally recommends therapy with a triple immunosuppressive regimen consisting of pulse IV glucocorticoids followed by oral glucocorticoid taper plus: 1) mycophenolic acid analog (MPAA) plus belimumab; 2) MPAA plus calcineurin inhibitor (CNI); or 3) EuroLupus low-dose cyclophosphamide (CYC) plus belimumab followed by MPAA substituted for CYC after CYC is complete (fig. 2, below).
“An MPAA-based regimen is preferred over a cyclophosphamide-based regimen,” Dr. Askanase said. For high-grade proteinuria (≥3g/g), MPAA plus CNI is preferred, over belimumab-based regimen. For patients with significant extra-renal manifestations, belimumab is preferred over CNI. Given CYC and CNI was not studied in randomized controlled trials, it was not recommended as part of the guideline.
Dr. Askanase finally briefly reviewed the data from the randomized controlled trials of voclosporin (AURORA 1), belimumab (BLISS-LN) and obinutuzumab (NOBILITY). In subgroup analyses of the voclosporin trial, patients with class III and IV lupus nephritis had better odds ratio response, as compared to those with pure class V.8
For belimumab (BLISS-LN), subgroup analyses suggested patients with class III or IV lupus nephritis did better than Class III + V or IV + V and better than pure Class V.9 “Additionally, patients with high-grade proteinuria [UPC >3] did less well than those with lower proteinuria,” she said. “In contrast, in the obinutuzumab subgroup analysis, patients with higher grade proteinuria [UPC >3] did better than those with lower grade proteinuria.”
In Summary
This session provided attendees a practical approach to the application of the 2024 ACR Guideline for Lupus Nephritis. The role of urinary protein biomarkers to better predict treatment response and prognosis was discussed, which may be entering our clinics in a few short years.
“We define response to lupus nephritis in a proteinurocentric way,” Dr. Fava said. “Better biomarkers are coming. In the meantime, don’t let proteinuria fool you.”
Mithu Maheswaranathan, MD, is an assistant professor of medicine in the Division of Rheumatology at Duke University School of Medicine, Durham, N.C.
