Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

Abstract

Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin's B-cell lymphoma in 1997.In the last 15 years, it has emerged as a potent immunosuppressant for many immune-mediated diseases, beginning initially with rheumatoid arthritis, and now extending into several other fields, including clinical nephrology. Based on recent large clinical trials, it is FDA-approved for the treatment of ANCA-associated vasculitis and continues to be studied in off-label usage for many glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in nephrotic syndrome in children and adults, including both minimal change disease and focal segmental glomerulosclerosis. Given its efficacy, tolerability and safety profile in comparison to more conventional treatment regimens, RTX is rapidly emerging as a critical treatment modality in glomerular disease.

Lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients

“…It has been used as a treatment for ANCA-associated vasculitis, membranous nephropathy, lupus nephritis, mixed cryoglobulinemia, and nephrotic syndrome caused by minimal change disease and focal segmental glomerulosclerosis in children and adults. 34 However, the mechanism of beneficial effects by B cell depletion is poorly understood and often occurs independently of autoantibody levels. It is of note that B cells can act both as regulators and drivers of autoimmune pathogenesis through production of cytokines.…”

Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study

“…Indeed, patients whose manifestations are not appropriate for (or insufficiently controlled by) antiviral or conventional immunosuppressive treatment may respond to RTX [5,7] . This is usually the case of patients with progressive renal failure, digital ischemia, gastrointestinal vasculitis or severe neuropathy.…”

“…The CR rate for nephropathy (as well as neuropathy) was 39%. This scheme, which was designed for patients thought to be too compromised to receive a standard dose [41] , is not recommended for cryoglobulinemic nephritis [7] .…”

Rituximab-induced remission in a woman with coexisting rheumatoid arthritis and nephrotic syndrome

“…Moreover, rituximab has been introduced as an emerging therapeutic agent to treat immune-mediated glomerular diseases including idiopathic membranous nephropathy [13]. Several reports reviewing single case reports and case series of rituximab use in idiopathic and secondary membranous nephropathy concluded that the efficacy seems promising particularly in light of the absence of side effects so commonly encountered with the use of alkylating agents [2,3,5,7,14].…”