Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy
In the MENTOR trial, rituximab was noninferior to cyclosporine for inducing remission of proteinuria in membranous nephropathy at 12 months and superior for maintaining remission through 24 months.
Background
Membranous nephropathy is a leading cause of nephrotic syndrome in adults, and B-cell abnormalities contribute to its pathogenesis. Calcineurin inhibitors such as cyclosporine reduce proteinuria but are associated with a high relapse rate after withdrawal. MENTOR tested whether B-cell depletion with rituximab was noninferior to cyclosporine for inducing and maintaining remission.
Study design
In this randomized trial, 130 patients with membranous nephropathy, proteinuria of at least 5 g per 24 hours, and preserved creatinine clearance who had received renin-angiotensin system blockade were assigned to intravenous rituximab (two 1000 mg infusions 14 days apart, repeated at 6 months for partial responders) or oral cyclosporine for 12 months. The primary outcome was complete or partial remission of proteinuria at 24 months, with patients followed for 24 months.
Key findings
At 12 months, 60% of the rituximab group and 52% of the cyclosporine group had complete or partial remission (risk difference 8 percentage points; P=0.004 for noninferiority). At 24 months, 60% of the rituximab group versus 20% of the cyclosporine group remained in remission (risk difference 40 percentage points, 95% CI 25 to 55; P<0.001 for both noninferiority and superiority). Anti-PLA2R antibody decline was faster and more durable with rituximab, and serious adverse events occurred in 17% of the rituximab group versus 31% of the cyclosporine group.
Clinical implications
MENTOR established rituximab as noninferior to cyclosporine for inducing remission and superior for maintaining it, with a favorable durability and safety profile. The findings reshaped treatment guidance for membranous nephropathy, positioning B-cell-targeted therapy as a preferred option over calcineurin inhibitors for many patients.
Category
Research
Source
N Engl J Med
More from ASNRT News
Browse the latest news, society announcements, KDIGO guideline updates, and AJNT issue releases on the ASNRT newsroom.