Rituximab therapy in idiopathic membranous nephropathy: a 2-year study.
OBJECTIVE
It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment.


METHODS
Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m(2) × 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations.


RESULTS
Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m(2) at baseline to 88.4 ml/min per 1.73 m(2) at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX.


CONCLUSIONS
Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.
Fervenza
Fernando C
FC
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55901, USA. fervenza.fernando@mayo.edu
Abraham
Roshini S
RS
Erickson
Stephen B
SB
Irazabal
Maria Valentina
MV
Eirin
Alfonso
A
Specks
Ulrich
U
Nachman
Patrick H
PH
Bergstralh
Eric J
EJ
Leung
Nelson
N
Cosio
Fernando G
FG
Hogan
Marie C
MC
Dillon
John J
JJ
Hickson
LaTonya J
LJ
Li
Xujian
X
Cattran
Daniel C
DC
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D016516:CD4-CD8 Ratio; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000069283:Rituximab