Rituximab Superior to Cyclosporine for Membranous Nephropathy Save

The NEJM has reported that rituximab (RTX) and cyclosporine (CYA) was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. 

The study enrolled 130 patients with membranous nephropathy, proteinuria of > 5 g per 24 hours, and a creatinine clearance of > 40 ml per minute per 1.73 m2 of body-surface area.  Patients were on background ACE inhibitors and were randomized to receive at least 3 months of intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). The primary outcome was a composite of complete or partial remission of proteinuria at 24 months.

The results at 12 months showed a complete or partial remission:

• RTX = 60%
• CyA = 52%

These results were compatible with noninferiority (risk difference, 8 percentage points; 95% confidence interval [CI], −9 to 25; P=0.004 for noninferiority).

The rate of complete or partial remission at 24 months:

• RTX = 60%
• CyA = 20%

in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority).

Among patients in remission who tested positive for anti–phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group.

There was a trend towards fewer serious adverse events with RTX (17%) compared to CyA (31%) (P=0.06).

Membranous glomerulonephritis appears to respond well to B-cell depletion with rituximab as it is noninferior to cyclosporine for inducing complete or partial remission of proteinuria over 12 mos but is superior ovr 24 mos and has fewer adverse effects.