Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Primary Membranous Nephropathy : A Case Series
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
RATIONALE & OBJECTIVE: Rituximab is the first-choice therapy for patients with primary membranous nephropathy (MN) and nephrotic syndrome. However, approximately 30% of patients are treatment-resistant or become treatment-intolerant with hypersensitivity reactions upon repeated drug exposures. We aimed to assess whether ofatumumab, a fully human second-generation anti-CD20 antibody, could be a valuable alternative to rituximab in this population.
STUDY DESIGN: Case series.
SETTING & PARTICIPANTS: 7 rituximab-intolerant and 10 rituximab-resistant patients with MN who consented to receive ofatumumab (50-300mg, single intravenous infusion) and were followed at the nephrology unit of Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII (Bergamo, Italy) between September 2015 and January 2019.
FINDINGS: Over a median (IQR) follow-up of 5.0 (3.0-9.8) months, all 7 rituximab-intolerant and 3 of the 10 rituximab-resistant patients exhibited complete (proteinuria<0.3g/d) or partial (proteinuria<3.5g/d with≥50% reduction vs baseline) remission of nephrotic syndrome. Circulating B cells were similarly depleted in all patients by 1 week, and serum anti-phospholipase A2 receptor antibody concentrations decreased to<2.7 relative units/mL in 3 of 4 rituximab-intolerant and 4 of 8 rituximab-resistant patients with phospholipase A2 receptor-related disease. Ofatumumab significantly reduced 24-hour urinary protein and immunoglobulin G excretion and increased serum albumin and immunoglobulin G levels. These effects were greater in rituximab-intolerant than in rituximab-resistant patients. Measured glomerular filtration rate significantly increased by an average of 13.4% at 24 months compared with baseline (P=0.036) among all patients in the series. There were 14 nonserious infusion-related adverse events in 9 patients that recovered with temporary infusion interruption.
LIMITATIONS: Retrospective design, limited number of patients.
CONCLUSIONS: Ofatumumab may represent an effective and safe treatment for rituximab-intolerant cases of MN. Larger prospective studies will be needed to validate these preliminary findings and explore the effectiveness of other second-generation anti-CD20 antibodies in this clinical setting.
PLAIN-LANGUAGE SUMMARY: Primary membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome (NS) in adults. In this case series, we explored the efficacy of ofatumumab, a fully human second-generation anti-CD20 antibody, in 17 patients with MN and NS who were intolerant or unresponsive to rituximab. All 7 rituximab-intolerant patients exhibited complete or partial clinical remission, compared with only 3 of the 10 rituximab-resistant patients. Autoantibody levels decreased in all patients with phospholipase A2 receptor-related disease. Ofatumumab achieved a significant reduction in urinary protein and immunoglobulin G excretion while increasing serum albumin and immunoglobulin G levels. Ofatumumab may be a promising option for patients with MN who are rituximab-intolerant. Further investigations are warranted to validate these preliminary findings.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
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| Enthalten in: |
American journal of kidney diseases : the official journal of the National Kidney Foundation - 83(2024), 3 vom: 25. Feb., Seite 340-349.e1 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Podestà, Manuel Alfredo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.02.2024 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1053/j.ajkd.2023.08.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Podestà, Manuel Alfredo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Primary Membranous Nephropathy |b A Case Series |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 26.02.2024 | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a RATIONALE & OBJECTIVE: Rituximab is the first-choice therapy for patients with primary membranous nephropathy (MN) and nephrotic syndrome. However, approximately 30% of patients are treatment-resistant or become treatment-intolerant with hypersensitivity reactions upon repeated drug exposures. We aimed to assess whether ofatumumab, a fully human second-generation anti-CD20 antibody, could be a valuable alternative to rituximab in this population | ||
| 520 | |a STUDY DESIGN: Case series | ||
| 520 | |a SETTING & PARTICIPANTS: 7 rituximab-intolerant and 10 rituximab-resistant patients with MN who consented to receive ofatumumab (50-300mg, single intravenous infusion) and were followed at the nephrology unit of Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII (Bergamo, Italy) between September 2015 and January 2019 | ||
| 520 | |a FINDINGS: Over a median (IQR) follow-up of 5.0 (3.0-9.8) months, all 7 rituximab-intolerant and 3 of the 10 rituximab-resistant patients exhibited complete (proteinuria<0.3g/d) or partial (proteinuria<3.5g/d with≥50% reduction vs baseline) remission of nephrotic syndrome. Circulating B cells were similarly depleted in all patients by 1 week, and serum anti-phospholipase A2 receptor antibody concentrations decreased to<2.7 relative units/mL in 3 of 4 rituximab-intolerant and 4 of 8 rituximab-resistant patients with phospholipase A2 receptor-related disease. Ofatumumab significantly reduced 24-hour urinary protein and immunoglobulin G excretion and increased serum albumin and immunoglobulin G levels. These effects were greater in rituximab-intolerant than in rituximab-resistant patients. Measured glomerular filtration rate significantly increased by an average of 13.4% at 24 months compared with baseline (P=0.036) among all patients in the series. There were 14 nonserious infusion-related adverse events in 9 patients that recovered with temporary infusion interruption | ||
| 520 | |a LIMITATIONS: Retrospective design, limited number of patients | ||
| 520 | |a CONCLUSIONS: Ofatumumab may represent an effective and safe treatment for rituximab-intolerant cases of MN. Larger prospective studies will be needed to validate these preliminary findings and explore the effectiveness of other second-generation anti-CD20 antibodies in this clinical setting | ||
| 520 | |a PLAIN-LANGUAGE SUMMARY: Primary membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome (NS) in adults. In this case series, we explored the efficacy of ofatumumab, a fully human second-generation anti-CD20 antibody, in 17 patients with MN and NS who were intolerant or unresponsive to rituximab. All 7 rituximab-intolerant patients exhibited complete or partial clinical remission, compared with only 3 of the 10 rituximab-resistant patients. Autoantibody levels decreased in all patients with phospholipase A2 receptor-related disease. Ofatumumab achieved a significant reduction in urinary protein and immunoglobulin G excretion while increasing serum albumin and immunoglobulin G levels. Ofatumumab may be a promising option for patients with MN who are rituximab-intolerant. Further investigations are warranted to validate these preliminary findings | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a Rituximab | |
| 650 | 4 | |a membranous nephropathy | |
| 650 | 4 | |a nephrotic syndrome | |
| 650 | 4 | |a ofatumumab | |
| 650 | 7 | |a Rituximab |2 NLM | |
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| 650 | 7 | |a ofatumumab |2 NLM | |
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| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Serum Albumin |2 NLM | |
| 650 | 7 | |a Phospholipases |2 NLM | |
| 650 | 7 | |a EC 3.1.- |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Receptors, Phospholipase A2 |2 NLM | |
| 700 | 1 | |a Trillini, Matias |e verfasserin |4 aut | |
| 700 | 1 | |a Portalupi, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Gennarini, Alessia |e verfasserin |4 aut | |
| 700 | 1 | |a Tomatis, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Villa, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Perna, Annalisa |e verfasserin |4 aut | |
| 700 | 1 | |a Rubis, Nadia |e verfasserin |4 aut | |
| 700 | 1 | |a Remuzzi, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Ruggenenti, Piero |e verfasserin |4 aut | |
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