High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy.

Abstract

BACKGROUND AND OBJECTIVES\nDifferent rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.\n\n\nDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS\nTwenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at two-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m2 at one-week interval. We measured serum rituximab levels and compared remission at month six and before any treatment modification and analyzed factors associated with remission and relapses.\n\n\nRESULTS\nRemissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (P=0.02) at month six, respectively, and in 24 (86%) versus 18 (67%) participants (P=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3-9] and 9 [IQR, 6-12] months for NICE and GEMRITUX cohorts respectively (P=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0-10.8] versus 0.0 [IQR, 0.0-0.0] P<0.001 and 0.0 [IQR, 0.0-2.0] versus 16.5 [IQR, 2.5-31.0] P<0.001) at month three, lower level of anti-PLA2R1 antibodies at month six (0.0 [IQR, 0.0-8.0] versus 8.3 [IQR, 0.0-73.5] P=0.03). In the combined study population, lower epitope spreading at diagnosis and higher rituximab levels at month three were associated with remissions at month six (13/26 (50%) versus 22/29 (76%) P=0.05 and 2.2 µg/ml [IQR, 0.0-10.9] versus 0.0 µg/ml [IQR, 0.0-0.0] P<0.001 respectively). All non-spreaders entered into remission whatever the protocol. Eight of the 41 participants who reached remission had relapses. Epitope spreading at diagnosis (8/8 (100%) versus 16/33 (48%) P=0.01) and incomplete depletion of anti-PLA2R1 antibodies at month six (4/8 (50%) versus 5/33 (9%) P=0.05) were associated with relapses.\n\n\nCONCLUSIONS\nOur work suggests that higher dose rituximab protocol is more effective on depletion of B-cells and lack of epitope spreading is associated with remission of membranous nephropathy.