期刊
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 14, 期 8, 页码 1173-1182出版社
AMER SOC NEPHROLOGY
DOI: 10.2215/CJN.11791018
关键词
membranous nephropathy; clinical immunology; Humans; Rituximab; lomerulonephritis; Membranous; B-lymphocytes; Cohort Studies; Recurrence; Epitopes
资金
- Centre Hospitalier Universitaire de Nice
- Direction generale de l'Offre de soins of the French Ministry of Health [PHRC2011-A01302-39, NCT01897961]
- National Research Agency (ANR) through the Investments for the Future LABEX SIGNALIFE programme (MNaims) [ANR-17-CE17-0012-01]
- Fondation pour la Recherche Medicale [FRMING20140129210, SPF20150934219, FDT201805005509, DEQ20180339193]
- European Research Council [ERC-2012-ADG_20120314, 322947]
- Seventh Framework Programme of the European Community [2012-305608]
- Les Amis de la faculte de medecine de Nice
- National Research Agency (ANR) through the Investments for the Future LABEX SIGNALIFE programme [ANR-11-LABX-0028-01]
- Assistance Publique-Hopitaux de Paris (Departement de la Recherche Clinique et du Developpement) [NCT01508468]
- Centre Hospitalier de Nice [NCT02199145]
- FHU Oncoage, Nice
- CNRS
Background and objectivesDifferent rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.Design, setting, participants, & measurementsTwenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-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/m(2) at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses.ResultsRemissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (P=0.02) at month 6, 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 mu g/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 3, lower level of anti-PLA2R1 antibodies at month 6 (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 3 were associated with remissions at month 6 (13/26 (50%) versus 22/29 (76%) P=0.05 and 2.2 mu g/ml [IQR, 0.0-10.9] versus 0.0 mu g/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 6 (4/8 (50%) versus 5/33 (9%) P=0.05) were associated with relapses.ConclusionsOur 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.
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