Rituximab in treatment of idiopathic glomerulopathy

Abstract

The aim of our study was to assess the role of rituximab (Mabthera) in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD) group, 31 of the 32 patients had complete remission (CR) and were off any immunosuppressive therapy and one of the previous non-responders (NR) did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months). Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS), while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab. The drug is effective and safe for treatment of patients refractory to the conventional agents.

Single dose of rituximab in children with steroid-dependent minimal change nephrotic syndrome

“…Long-term use and a high dose of steroids and immunosuppressants cause severe side effects (3). Thus, oral agent-free treatment is an attractive therapeutic approach for patients with nephrotic syndrome (21). The role of B lymphocytes in the pathogenesis of MCD, a T-cell, has been previously considered to play a key role (22)(23)(24)(25)(26).…”

Rituximab Treatment for Relapsing Minimal Change Disease and Focal Segmental Glomerulosclerosis: A Systematic Review

“…Self-limiting infusion-related adverse events were observed in nearly 40% of patients treated with RTX [35,45]. Late-onset adverse events attributed to RTX therapy including late-onset neutropenia [46], progressive multifocal leukoencephalopathy [47] or RTX-associated lung disease [48] are rare, but fatalities have been reported.…”

“…However, 1 patient presented with bronchopneumonia [35] 2 months after RTX infusions, and bloody diarrhea [45] was observed in another patient after treatment. Since no randomized controlled trials in adults have been performed to date, severe adverse events might be underestimated by these reports.…”

Rituximab in Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis

“…All adult patients remained in remission, whereas the rate of relapses and steroid use could be reduced significantly [3]. Another prospective study revealed a good response after RTX in patients with steroid-resistant forms of MCD and FSGS, although important clinical information is missing in this instead of that report [13]. We performed an analysis of the reported data on steroid-dependent and multirelapsing MCD and FSGS including 86 patients to elucidate factors influencing therapeutic responses towards RTX.…”

“…All patients received concomitant immunosuppressive medication at the time of side-effect onset. In a prospective study treating diverse glomerulonephritis, 5 patients did not tolerate RTX and were excluded from the study [13]. Among the included patients, infusion-related symptoms were frequent (itching, hypotension or bronchospasm).…”