Titrating Rituximab to Circulating B Cells to Optimize Lymphocytolytic Therapy in Idiopathic Membranous Nephropathy

Abstract

Background and Objectives: Rituximab, given in four weekly doses, is a promising treatment for idiopathic membranous nephropathy and other immune-mediated diseases and lymphoproliferative disorders. This multidose regimen, however, may cause hypersensitivity reactions and is extremely expensive. This study was aimed at evaluating whether titrating rituximab to circulating CD20 B cells may improve safety and limit costs of treatment.

Design, Setting, Participants, & Measurements: In a matched-cohort, single-center, controlled study, the outcome of 12 new incident patients who had idiopathic membranous nephropathy and nephrotic syndrome and received a B cell–driven treatment was compared with that of 24 historical reference patients who were given the standard protocol of four weekly doses of 375 mg/m².

Results: Only one patient needed a second dose to achieve full CD20 cell depletion. At 1 yr, time course of the components of nephrotic syndrome and the proportion of patients who achieved disease remission (25%) was identical in both groups. Persistent CD20 cell depletion was achieved in all patients. Costs for rituximab treatment and hospitalizations totalled €3770.90 ($4902.20) and €13,977.60 ($18,170.80) with the B cell–driven and the four-dose protocol, respectively. One patient on standard protocol had a severe adverse reaction at second rituximab dose. Thus, B cell titrated as effectively as standard rituximab treatment achieves B cell depletion and idiopathic membranous nephropathy remission but is fourfold less expensive, allowing for more than €10,000, approximately $13,000 in savings per patient.

Conclusions: Avoiding unnecessary reexposure to rituximab is extremely cost-saving and may limit the production of antichimeric antibodies that may increase the risk for adverse reactions and prevent re-treatment of disease recurrences.