Lupus Nephritis Treatment Consensus and Future Directions

Lupus nephritis (LN) develops in as many as two-thirds of patients with systemic lupus erythematosus (SLE) within 5 years of SLE onset. Once LN occurs, it is associated with worse morbidity, health-related quality of life, and mortality. Kidney failure is a major concern.

“ESKD still develops in 5 to 30% of patients with LN within 10 years of diagnosis, suggesting an unmet need to improve the efficacy-to-toxicity balance of current therapeutics,” Chi Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, China, and colleagues noted in a recent review published in Nature Reviews Rheumatology.

The authors wrote the review to outline current and potential treatments for LN, consensus, and future directions.

Standard of Care

LN guidelines vary among countries due to differences in ethnic makeup and available resources, according to the authors. Hydroxychloroquine is universally recommended for initial therapy but requires dosage adjustment in patients with low estimated glomerular filtration rate (eGFR).

Guidelines from major rheumatology and nephrology associations agree that conventional induction therapies for severe LN include high doses of glucocorticoids with either cyclophosphamide or mycophenolate mofetil (MMF). Dosages vary, however, due to concerns over toxicity. In the full review, the authors compared and contrasted guideline recommendations for patients with class 3 and 4, pure class 5, and refractory LN.

Tacrolimus, a calcineurin inhibitor, is recommended as second-line therapy for LN in Asian patients who cannot tolerate cyclophosphamide or MMF. Rituximab, a B cell-targeted therapy, is recommended for rescue therapy. Maintenance therapy for LN should continue for 3 to 5 years to minimize renal flares. All major guidelines recommend MMF or azathioprine for maintenance therapy, and some suggest a low-dose calcineurin inhibitor as an alternative.

As yet, there is no consensus on treating patients with rapidly progressive LN, such as crescents or fibrinoid necrosis.

Cessation of maintenance therapy is still being debated. A randomized controlled trial (Clinicaltrials.gov NCT04449991) is currently investigating whether histological remission on a repeat renal biopsy suffices for treatment discontinuation.

Novel Therapeutics

Clinical trials are investigating novel biological agents or targeted small molecules in combination with standard of care in LN. New-generation anti-CD20 biologic agents, type I interferon antagonists, and rituximab-belimumab combination regimens show promise, according to the authors.

Voclosporin, a novel calcineurin inhibitor, induces renal response when added to standard of care MMF and glucocorticoids, with no increased risk of infection. Voclosporin is not recommended for patients with an eGFR of 45 mL/min/1.73 m² or less or in combination with cyclophosphamide.

Belimumab, a monoclonal antibody against B cell activating factor (BAFF), was tested as an add-on therapy to standard regimens of glucocorticoids plus MMF or cyclophosphamide plus azathioprine. Belimumab increased renal response and decreased the risk of renal flares and eGFR decline. The drug was less effective in patients with membranous LN, a urinary protein to creatinine ratio greater than 3.0, or Asian or African ancestry. It was also less effective with cyclophosphamide treatment.

Other steroid-sparing, B cell-targeting regimens under investigation include rituximab plus MMF and obinutuzumab, a newer generation anti-CD20 biologic, plus MMF.

This article originally appeared on Renal and Urology News