Rituximab aids remission in idiopathic membranous nephropathy

By Andrew Czyzewski, MedWire Reporter

Rituximab achieves good rates of remission in patients with persistent idiopathic membranous nephropathy (IMN), with few serious adverse events, study results show.

Rituximab was also effective when previous treatments with steroids and other immunosuppressive drugs had failed or a second course of rituximab was needed to treat disease recurrence after initial remission.

"By and large, the findings support the notion that rituximab therapy is at least as effective and remarkably safer than immunosuppressive regimens including steroids and alkylating agents," Giuseppe Remuzzi (Mario Negri Institute for Pharmacological Research, Bergamo, Italy) and colleagues comment in the Journal of the American Society of Nephrology.

Around 10% of patients with persistent nephrotic syndrome die prematurely of cardiovascular events before progressing to end-stage renal disease (ESRD). Immunosuppressive regimens can reduce this rate but carry an increased risk for lymphoproliferative disorders, cancer, infections, myelotoxicity, iatrogenic diabetes, and other serious adverse events.

In the current study, the researchers performed a trial of the monoclonal antibody rituximab, which selectively depletes B lymphocytes, in 100 consecutive IMN patients with persistent nephrotic syndrome.

Before referral, 32 patients had already been treated at other institutions with steroids alone or in combination with alkylating agents, calcineurin inhibitors, or other immunosuppressants.

After a median follow-up of 29 months after rituximab administration, 27 patients achieved complete remission, defined as 24-hour urinary protein excretion of less than 0.3 g, while 38 achieved partial remission (persistent proteinuria <3 g/24 h).

Of the 35 patients who did not achieve the combined endpoint, 20 of them did nevertheless show a reduction in urinary protein excretion of at least 50% from baseline.

Notably, the rates of remission were similar between patients with or without previous immunosuppressive treatment.

Rituximab was well tolerated and no treatment-related serious events were observed throughout the whole study period.

There were 11 patients who developed serious adverse events, seven in the group without remission and three and one in the groups with partial and complete remission, respectively. Eight events were from cardiovascular causes while one patient died from stroke at 83 years of age and two died from acute myocardial infarction when both were aged 79 years.

"Altogether, the above findings converge to indicate that rituximab has a remarkably good risk-benefit profile for the treatment of IMN and that disease remission achieved by rituximab treatment, in addition to prevent[ing] terminal kidney failure, may also help reduce the excess cardiovascular risk in this population, particularly in most severe forms," Remuzzi et al comment.

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