Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy.
OBJECTIVE
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.


METHODS
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membranous nephropathy and nephrotic syndrome and received a B cell-driven treatment was compared with that of 24 historical reference patients who were given the standard protocol of four weekly doses of 375 mg/m2.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 euros ($4902.20) and 13,977.60 euros ($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 euros, 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.
Cravedi
Paolo
P
Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Italy.
Ruggenenti
Piero
P
Sghirlanzoni
Maria Chiara
MC
Remuzzi
Giuseppe
G
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes; D015331:Cohort Studies; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab