Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies

Introduction: Although rituximab has significantly improved outcomes for patients with membranous nephropathy, response to treatment is not universal and drug resistance can occur. One mechanism of resistance is the occurrence of antidrug antibodies. Obinutuzumab and ofatumumab are humanized and hum...

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Main Authors: Maxime Teisseyre, Marco Allinovi, Vincent Audard, Marion Cremoni, Giulia Belvederi, Alexandre Karamé, Matteo Accinno, Julien Duquesne, Vinod Sharma, Céline Fernandez, Kévin Zorzi, Mounir El Maï, Vesna Brglez, Sylvia Benzaken, Vincent L.M. Esnault, Alessandra Vultaggio, Harbir Singh Kohli, Raja Ramachandran, Calogero Lino Cirami, Barbara Seitz-Polski
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924034132
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author Maxime Teisseyre
Marco Allinovi
Vincent Audard
Marion Cremoni
Giulia Belvederi
Alexandre Karamé
Matteo Accinno
Julien Duquesne
Vinod Sharma
Céline Fernandez
Kévin Zorzi
Mounir El Maï
Vesna Brglez
Sylvia Benzaken
Vincent L.M. Esnault
Alessandra Vultaggio
Harbir Singh Kohli
Raja Ramachandran
Calogero Lino Cirami
Barbara Seitz-Polski
author_facet Maxime Teisseyre
Marco Allinovi
Vincent Audard
Marion Cremoni
Giulia Belvederi
Alexandre Karamé
Matteo Accinno
Julien Duquesne
Vinod Sharma
Céline Fernandez
Kévin Zorzi
Mounir El Maï
Vesna Brglez
Sylvia Benzaken
Vincent L.M. Esnault
Alessandra Vultaggio
Harbir Singh Kohli
Raja Ramachandran
Calogero Lino Cirami
Barbara Seitz-Polski
author_sort Maxime Teisseyre
collection DOAJ
description Introduction: Although rituximab has significantly improved outcomes for patients with membranous nephropathy, response to treatment is not universal and drug resistance can occur. One mechanism of resistance is the occurrence of antidrug antibodies. Obinutuzumab and ofatumumab are humanized and human monoclonal antibodies, respectively, that target B cells. These treatments have been shown to be effective in membranous nephropathy. However, obinutuzumab and ofatumumab have never been compared with rituximab in the treatment of patients with membranous nephropathy with anti-rituximab antibodies. We aimed to compare the efficacy and safety of obinutuzumab and ofatumumab with rituximab in patients with membranous nephropathy with anti-rituximab antibodies. Methods: This international retrospective multicenter study enrolled 34 patients with membranous nephropathy from 5 nephrology departments in France, India, and Italy. All the patients had previously developed anti-rituximab antibodies. Nineteen patients received rituximab, 12 received obinutuzumab, and 3 received ofatumumab. Results: Patients treated with obinutuzumab or ofatumumab were more likely to achieve clinical remission than those treated with rituximab at month 6 (87% vs. 37%, P = 0.005) and month 12 (87% vs. 42%, P = 0.01). Patients treated with obinutuzumab or ofatumumab were more likely to achieve immunological remission and B-cell depletion at month 6 than the patients treated with rituximab (92% vs. 56%, P = 0.04 and 93% vs. 35%, P = 0.002, respectively). No serious adverse events were reported in the obinutuzumab or ofatumumab group. Conclusion: Obinutuzumab and ofatumumab are more effective than rituximab in treating patients with membranous nephropathy with anti-rituximab antibodies. Anti-rituximab antibodies should be systematically monitored, to determine appropriate treatment.
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spelling doaj-art-d6e07306f9314ecd835d2e81b5a9596f2025-08-20T03:45:08ZengElsevierKidney International Reports2468-02492025-03-0110375376110.1016/j.ekir.2024.12.012Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab AntibodiesMaxime Teisseyre0Marco Allinovi1Vincent Audard2Marion Cremoni3Giulia Belvederi4Alexandre Karamé5Matteo Accinno6Julien Duquesne7Vinod Sharma8Céline Fernandez9Kévin Zorzi10Mounir El Maï11Vesna Brglez12Sylvia Benzaken13Vincent L.M. Esnault14Alessandra Vultaggio15Harbir Singh Kohli16Raja Ramachandran17Calogero Lino Cirami18Barbara Seitz-Polski19French Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Immunology Laboratory, Nice University Hospital, Université Côte d’Azur, Nice, France; Department of Nephrology, Dialysis and Transplantation, Nice University Hospital, Université Côte d’Azur, Nice, France; Unité de Recherche Clinique Côte d’Azur, Université Côte d’Azur, Nice, France; Correspondence: Maxime Teisseyre, Immunology Department, Hôpital de l’Archet 1, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Route de Ginestière, Nice, France.Department of Nephrology, Dialysis and Transplantation, Careggi University Hospital, Florence, ItalyFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Assistance Publique des Hôpitaux de Paris, Henri-Mondor University Hospital, Créteil, France; Department of Nephrology, Dialysis and Transplantation, Assistance Publique des Hôpitaux de Paris, Henri-Mondor University Hospital, Créteil, France; Paris Est Créteil University, Institut National de la Santé et de la Recherche Médicale U955, Institut Mondor de Recherche Biomédicale, Créteil, FranceFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Immunology Laboratory, Nice University Hospital, Université Côte d’Azur, Nice, France; Department of Nephrology, Dialysis and Transplantation, Nice University Hospital, Université Côte d’Azur, Nice, France; Unité de Recherche Clinique Côte d’Azur, Université Côte d’Azur, Nice, FranceDepartment of Nephrology, Dialysis and Transplantation, Careggi University Hospital, Florence, ItalyDepartment of Nephrology and Dialysis, Néphropôle - Médipole Hôpital Privé, Lyon-Villeurbanne, Villeurbanne, FranceDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Pharmacy, Nice University Hospital, Université Côte d’Azur, Nice, FranceDepartment of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Unité de Recherche Clinique Côte d’Azur, Université Côte d’Azur, Nice, FranceFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Department of Nephrology, Dialysis and Transplantation, Nice University Hospital, Université Côte d’Azur, Nice, France; Unité de Recherche Clinique Côte d’Azur, Université Côte d’Azur, Nice, FranceImmunology Laboratory, Nice University Hospital, Université Côte d’Azur, Nice, FranceFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Immunology Laboratory, Nice University Hospital, Université Côte d’Azur, Nice, France; Unité de Recherche Clinique Côte d’Azur, Université Côte d’Azur, Nice, FranceImmunology Laboratory, Nice University Hospital, Université Côte d’Azur, Nice, FranceFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Department of Nephrology, Dialysis and Transplantation, Nice University Hospital, Université Côte d’Azur, Nice, FranceDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Immunoallergology Unit, Careggi University Hospital, Florence, ItalyDepartment of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Nephrology, Dialysis and Transplantation, Careggi University Hospital, Florence, ItalyFrench Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France; Immunology Laboratory, Nice University Hospital, Université Côte d’Azur, Nice, France; Department of Nephrology, Dialysis and Transplantation, Nice University Hospital, Université Côte d’Azur, Nice, France; Unité de Recherche Clinique Côte d’Azur, Université Côte d’Azur, Nice, FranceIntroduction: Although rituximab has significantly improved outcomes for patients with membranous nephropathy, response to treatment is not universal and drug resistance can occur. One mechanism of resistance is the occurrence of antidrug antibodies. Obinutuzumab and ofatumumab are humanized and human monoclonal antibodies, respectively, that target B cells. These treatments have been shown to be effective in membranous nephropathy. However, obinutuzumab and ofatumumab have never been compared with rituximab in the treatment of patients with membranous nephropathy with anti-rituximab antibodies. We aimed to compare the efficacy and safety of obinutuzumab and ofatumumab with rituximab in patients with membranous nephropathy with anti-rituximab antibodies. Methods: This international retrospective multicenter study enrolled 34 patients with membranous nephropathy from 5 nephrology departments in France, India, and Italy. All the patients had previously developed anti-rituximab antibodies. Nineteen patients received rituximab, 12 received obinutuzumab, and 3 received ofatumumab. Results: Patients treated with obinutuzumab or ofatumumab were more likely to achieve clinical remission than those treated with rituximab at month 6 (87% vs. 37%, P = 0.005) and month 12 (87% vs. 42%, P = 0.01). Patients treated with obinutuzumab or ofatumumab were more likely to achieve immunological remission and B-cell depletion at month 6 than the patients treated with rituximab (92% vs. 56%, P = 0.04 and 93% vs. 35%, P = 0.002, respectively). No serious adverse events were reported in the obinutuzumab or ofatumumab group. Conclusion: Obinutuzumab and ofatumumab are more effective than rituximab in treating patients with membranous nephropathy with anti-rituximab antibodies. Anti-rituximab antibodies should be systematically monitored, to determine appropriate treatment.http://www.sciencedirect.com/science/article/pii/S2468024924034132antidrug antibodiesimmunomonitoringmembranous nephropathyobinutuzumabofatumumabrituximab
spellingShingle Maxime Teisseyre
Marco Allinovi
Vincent Audard
Marion Cremoni
Giulia Belvederi
Alexandre Karamé
Matteo Accinno
Julien Duquesne
Vinod Sharma
Céline Fernandez
Kévin Zorzi
Mounir El Maï
Vesna Brglez
Sylvia Benzaken
Vincent L.M. Esnault
Alessandra Vultaggio
Harbir Singh Kohli
Raja Ramachandran
Calogero Lino Cirami
Barbara Seitz-Polski
Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
Kidney International Reports
antidrug antibodies
immunomonitoring
membranous nephropathy
obinutuzumab
ofatumumab
rituximab
title Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
title_full Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
title_fullStr Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
title_full_unstemmed Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
title_short Obinutuzumab and Ofatumumab are More Effective Than Rituximab in the Treatment of Membranous Nephropathy Patients With Anti-Rituximab Antibodies
title_sort obinutuzumab and ofatumumab are more effective than rituximab in the treatment of membranous nephropathy patients with anti rituximab antibodies
topic antidrug antibodies
immunomonitoring
membranous nephropathy
obinutuzumab
ofatumumab
rituximab
url http://www.sciencedirect.com/science/article/pii/S2468024924034132
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