Rituximab in Idiopathic Membranous Nephropathy

Abstract

Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria ,0.3 g/24 h and partial remission as persistent proteinuria ,3 g/24 h, each also having .50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m 2 among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.

Glomerular Diseases

“…These are impressive results and no serious side effects were encountered. However, four patients died, three developed cancer, and four progressed to ESRD (47). Good results with rituximab have also been reported in another observational study conducted in North America.…”

“…Recently, these investigators reported their observational experience in 100 patients with MN treated with rituximab (47). After a mean follow-up of 29 months, 27 patients were in complete remission and 38 were in partial remission (total response rate of 65%).…”

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

“…In these patients, the duration of cyclophosphamide therapy is limited to 3 months, which results in a relatively safe cumulative dose of less than 10 g (27). Other drugs have been suggested as first-line treatment, such as mycophenolate mofetil, cyclosporin A, tacrolimus, and rituximab (28,29). Although these drugs induce remission of proteinuria, they have not been unequivocally shown to be as effective as cyclophosphamide in a direct comparison of long-term outcome.…”

“…Although these drugs induce remission of proteinuria, they have not been unequivocally shown to be as effective as cyclophosphamide in a direct comparison of long-term outcome. Moreover, mycophenolate mofetil and calcineurin inhibitors have been associated with malignancy in the transplantation setting, possibly through viral mediators (29). For rituximab, however, data on long-term risks are limited.…”

Balancing Cancer Risk and Efficacy of Using Cyclophosphamide to Treat Idiopathic Membranous Nephropathy

“…While MMF as monotherapy has not been shown to be effective (23), MMF in combination with steroids may induce remissions as effectively as alkylating agents; however, posttreatment relapse occurs in 75% of patients (24). Rituximab has been shown to induce remission in several studies to date (25)(26)(27), with decline in proteinuria occurring several months after dosing. Optimal dosing regimen, retreatment schedule, and long term effects, however, are yet to be corroborated by large trials.…”