High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy
Copyright © 2019 by the American Society of Nephrology..
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.
| Errataetall: |
CommentIn: Clin J Am Soc Nephrol. 2019 Aug 7;14(8):1122-1124. - PMID 31340980 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Clinical journal of the American Society of Nephrology : CJASN - 14(2019), 8 vom: 07. Aug., Seite 1173-1182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Seitz-Polski, Barbara [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.10.2020 Date Revised 02.05.2023 published: Print-Electronic ClinicalTrials.gov: NCT01508468, NCT02199145, NCT01897961 CommentIn: Clin J Am Soc Nephrol. 2019 Aug 7;14(8):1122-1124. - PMID 31340980 Citation Status MEDLINE |
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| doi: |
10.2215/CJN.11791018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 22.10.2020 | ||
| 500 | |a Date Revised 02.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01508468, NCT02199145, NCT01897961 | ||
| 500 | |a CommentIn: Clin J Am Soc Nephrol. 2019 Aug 7;14(8):1122-1124. - PMID 31340980 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 by the American Society of Nephrology. | ||
| 520 | |a BACKGROUND AND OBJECTIVES: Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B-lymphocytes | |
| 650 | 4 | |a Cohort Studies | |
| 650 | 4 | |a Epitopes | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Recurrence | |
| 650 | 4 | |a Rituximab | |
| 650 | 4 | |a clinical immunology | |
| 650 | 4 | |a lomerulonephritis, Membranous | |
| 650 | 4 | |a membranous nephropathy | |
| 650 | 7 | |a Immunologic Factors |2 NLM | |
| 650 | 7 | |a PLA2R1 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, Phospholipase A2 |2 NLM | |
| 650 | 7 | |a Rituximab |2 NLM | |
| 650 | 7 | |a 4F4X42SYQ6 |2 NLM | |
| 700 | 1 | |a Dahan, Karine |e verfasserin |4 aut | |
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| 700 | 1 | |a Rosenthal, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Benzaken, Sylvia |e verfasserin |4 aut | |
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| 700 | 1 | |a Esnault, Vincent L M |e verfasserin |4 aut | |
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