Update on Rituximab: An Established Treatment for All Immune-Mediated Kidney Diseases?

Abstract

Rituximab, a monoclonal antibody directed against the CD20 antigen, found on certain B-cell subsets, results in significant B-cell depletion and has been increasingly used in immune-mediated renal disease and transplantation. Although originally applied to what were considered antibody-mediated diseases, it has become clear that auto- and alloreactive B cells contribute in many ways to immune dysfunction, and the benefit of B-cell depletion extends beyond reduction in auto- or alloantibody levels. Most positive data regarding the benefit of rituximab in immune-mediated kidney disease have come from uncontrolled cohort studies, with the only positive controlled clinical trials demonstrating efficacy for the treatment of systemic vasculitis. While negative trials may have potentially missed clinical effects due to trial design, there may be significant differences in responses in different diseases or lack of efficacy due to therapeutic overlap when used with certain drug combinations. Rituximab is a novel treatment that provides a clear alternative for patients in different clinical situations, and allows for customization of therapy. However, much remains to be understood as to how best to use it in a cost-effective manner, when not to use it, and what the long-term impact of therapy may be.

Emerging therapies in immunoglobulin A nephropathy

“…Rituximab (Rituxan®, MabThera® and Zytux®), a chimeric monoclonal antibody directed against the CD20 antigen of B cells, causes B‐cell depletion and has proven efficacy in treating B cell lymphomas, leukaemias, transplant rejection and autoimmune disorders including SLE, rheumatoid arthritis, dermatomyositis and ANCA‐associated vasculitis . B cell depletion is clearly an attractive therapeutic approach in IgAN as this should switch off production of poorly galactosylated IgA1 and glycan‐specific IgG/IgA autoantibodies and limit the formation of circulating immune complexes.…”

Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials

“…[ 21 ], rituximab tends to be a safer therapeutic option in children with SDNS to maintain an adequate eGFR rate compared to tacrolimus. Moreover, the minimum eGFR values to start rituximab therapy were considerably low at 60 mL/min per 1.73 m 2 [ 25 26 ], thus demonstrating a better therapeutic window. The successful administration of rituximab as a safer and more effective corticosteroid-sparing therapy has raised a question of whether and when anti-B-cell therapy should be considered as the first-line regimen, to minimize corticosteroid exposure and avoid the nephrotoxic effects exerted by the CNI.…”

Efficacy of mycophenolate treatment in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome

“…In recent years, another immunosuppressive therapy that has been proposed for diverse immune-mediated diseases and also for SD/FR-INS is rituximab (RTX), a B-cell-depleting monoclonal antibody that targets CD20 [ 25 ]. This drug induces nephrotic remission in many of these patients as well, and its effect can persist over months, although nephrotic relapses are also frequently described, in some instances coinciding with B-cell population recovery [ 26 ].…”