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Clin J Am Soc Nephrol. 2019 Aug 7;14(8):1173-1182. doi: 10.2215/CJN.11791018. Epub 2019 Jul 24.

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

Author information

1
Department of Immunology, Hôpital l'Archet, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France; seitz-polski.b@chu-nice.fr.
2
Department of Nephrology-Dialysis-Transplantation, Hôpital Pasteur, CHU de Nice, Université Côte d'Azur, Nice, France.
3
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université Côte d'Azur, Nice, France.
4
Department of Nephrology and Dialysis, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Paris, France.
5
Unité Mixte de Recherche_S 1155, Institut National de la Santé et de la Recherche Médicale, Paris, France.
6
Sorbonne Université, Université Pierre et Marie Curie University Paris 06, Paris, France; and.
7
Department of Clinical Pharmacology and Clinical Research, Hôpital Saint Antoine, AP-HP, Paris, France.
8
Department of Immunology, Hôpital l'Archet, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.

Abstract

BACKGROUND AND OBJECTIVES:

Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

Twenty-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/m2 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.

RESULTS:

Remissions 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 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 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 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 6 (4/8 (50%) versus 5/33 (9%) P=0.05) were associated with relapses.

CONCLUSIONS:

Our 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.

KEYWORDS:

B-lymphocytes; Cohort Studies; Epitopes; Humans; Recurrence; Rituximab; clinical immunology; lomerulonephritis, Membranous; membranous nephropathy

PMID:
31340979
PMCID:
PMC6682825
[Available on 2020-08-07]
DOI:
10.2215/CJN.11791018

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