Rituximab, an anti-CD20 monoclonal antibody, is as effective as cyclosporine, a calcineurin inhibitor, in inducing proteinuria remission at 12 months in patients with membranous nephropathy and is superior in maintaining proteinuria remission for up to 24 months, according to a new study published in the New England Journal of Medicine.

In MENTOR (Membranous Nephropathy Trial of Rituximab), Fernando C. Fervenza, MD, PhD, of Mayo Clinic and colleagues randomly assigned 130 patients with nephrotic-range proteinuria (more than 5 g/24 h) despite renin-angiotensin system blockade and who had a creatinine clearance of at least 40 mL/min/1.73 m2 to receive intravenous rituximab or oral cyclosporine. A composite of complete or partial remission of proteinuria at 24 months was the primary outcome measure.

At 12 months, 60% of the rituximab group vs 52% of the cyclosporine group had a complete or partial proteinuria response. By 24 months, 60% of the rituximab group vs 20% of the cyclosporine group achieved the end point – a significant difference of 40 percentage points. A third (35%) of patients treated with rituximab had complete remission compared with none treated with cyclosporine at 24 months. The researchers attribute the superiority of rituximab to a lower risk for relapse.

In addition, among patients in remission with anti-phospholipase A2 receptor (PLA2R) antibodies, a larger, faster, and more enduring decline in autoantibodies occurred in patients treated with rituximab than cyclosporine.

Major adverse events occurred less frequently in the rituximab group. Grade 3 or higher events arose in 52% vs 68% of the rituximab and cyclosporine groups, respectively. Serious adverse events occurred in 17% vs 31%, respectively.

“Will anti-CD20 antibodies become the treatment of choice for all patients with membranous nephropathy? Probably not,” according to editorialists Piero Ruggenenti, MD, of Pope John XXIII Hospital, and Giuseppe Remuzzi, MD, of Mario Negri Institute for Pharmacological Research IRCCS, in Italy. “Rituximab therapy may fail in 25 to 30% of patients with nephrotic syndrome (owing to ineffective or transient depletion of nephritogenic antibodies or sensitization syndrome resembling serum sickness, which translates into resistance to treatment).” Instead, they suggested that some alternative drugs may prove more useful.

The trial was funded by Genentech, the makers of Rituxan (rituximab).

References

Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med. 381:36-46. doi:10.1056/NEJMoa1814427

Ruggenenti P, Remuzzi G. A First Step toward a New Approach to Treating Membranous Nephropathy. N Engl J Med. 381:86-88. doi:10.1056/NEJMe1906666