Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy
Introduction: Rituximab is a first-line treatment for primary membranous nephropathy (pMN), with proven efficacy and safety. The use of monoclonal antibodies such as rituximab can lead to the formation of antidrug antibodies that may interfere with the therapeutic response. In pMN, anti-rituximab an...
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Elsevier
2025-08-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024925002840 |
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| author | Marco Allinovi Maxime Teisseyre Matteo Accinno Cecilia Finocchi Vincent L.M. Esnault Marion Cremoni Tommaso Mazzierli Daniela Lazzarini Micaela Anna Casiraghi Céline Fernandez Kévin Zorzi Vesna Brglez Lorenzo Cosmi Andrea Matucci Leonardo Caroti Giulia Antognoli Calogero Lino Cirami Alessandra Vultaggio Barbara Seitz-Polski |
| author_facet | Marco Allinovi Maxime Teisseyre Matteo Accinno Cecilia Finocchi Vincent L.M. Esnault Marion Cremoni Tommaso Mazzierli Daniela Lazzarini Micaela Anna Casiraghi Céline Fernandez Kévin Zorzi Vesna Brglez Lorenzo Cosmi Andrea Matucci Leonardo Caroti Giulia Antognoli Calogero Lino Cirami Alessandra Vultaggio Barbara Seitz-Polski |
| author_sort | Marco Allinovi |
| collection | DOAJ |
| description | Introduction: Rituximab is a first-line treatment for primary membranous nephropathy (pMN), with proven efficacy and safety. The use of monoclonal antibodies such as rituximab can lead to the formation of antidrug antibodies that may interfere with the therapeutic response. In pMN, anti-rituximab antibodies (ARAs) have been shown to neutralize the cytotoxicity of rituximab, thereby increasing the risk of relapse of nephrotic syndrome. However, the kinetics of ARAs over time and the effect of ARA titer on prognosis are unclear. Methods: This retrospective international multicenter study included 74 patients with pMN treated with rituximab. Here we aimed to clarify the correlation between ARAs and clinical outcome, as well as to evaluate the most appropriate timing of ARA detection. Results: Overall, 35 out of 74 patients (47%) developed ARAs after a median of 9 (interquartile range: 6–12) months following rituximab administration. ARA monitoring at month-9, month-12 and before rituximab readministration identified 88% of patients with ARAs. Clinical remission rate at 6 and 12 months after rituximab administration was significantly lower in patients with ARAs (31% vs. 56%, P = 0.03 and 54% vs. 87%, P = 0.0017, respectively). ARAs were associated with a significantly higher rate of relapse (63% vs. 29%, P = 0.036) and a higher rate of B-cell reconstitution at 6 months (74.2% vs. 50%, P = 0.048). Notably, relapse occurred earlier in patients with ARAs (22 months vs. 32 months, P = 0.01). Conclusion: The development of ARAs represents one of the most important prognostic factors in pMN, being significantly associated with a reduced remission rate and a higher relapse rate after rituximab therapy. Alternative therapies with obinutuzumab or ofatumumab should be considered for these patients. |
| format | Article |
| id | doaj-art-ae11b16762cd44e4a35c680dfb3df3eb |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-ae11b16762cd44e4a35c680dfb3df3eb2025-08-20T03:33:31ZengElsevierKidney International Reports2468-02492025-08-011082621262910.1016/j.ekir.2025.04.059Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous NephropathyMarco Allinovi0Maxime Teisseyre1Matteo Accinno2Cecilia Finocchi3Vincent L.M. Esnault4Marion Cremoni5Tommaso Mazzierli6Daniela Lazzarini7Micaela Anna Casiraghi8Céline Fernandez9Kévin Zorzi10Vesna Brglez11Lorenzo Cosmi12Andrea Matucci13Leonardo Caroti14Giulia Antognoli15Calogero Lino Cirami16Alessandra Vultaggio17Barbara Seitz-Polski18Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, Italy; Correspondence: Marco Allinovi, Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, Italy.French 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; Institut de Recherche sur le Cancer et Vieillissement UMR7284 CNRS INSERM U1081, Université Côte d’Azur, Nice, France; Maxime Teisseyre, French Reference Center for Rare Diseases, Idiopathic Nephrotic Syndrome and Membranous Nephropathy, Nice University Hospital, Université Côte d’Azur, Nice, France.Department of Experimental and Clinical Medicine, University of Florence, Florence, ItalyNephrology, Dialysis and Transplantation Unit, 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; Department of Nephrology, Dialysis and Transplantation, 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; Department of Nephrology, Dialysis and Transplantation, Nice University Hospital, Université Côte d’Azur, Nice, France; Institut de Recherche sur le Cancer et Vieillissement UMR7284 CNRS INSERM U1081, Université Côte d’Azur, Nice, FranceNephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, ItalyNephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, ItalyNephrology, Dialysis and Transplantation Unit, 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; Institut de Recherche sur le Cancer et Vieillissement UMR7284 CNRS INSERM U1081, 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; Institut de Recherche sur le Cancer et Vieillissement UMR7284 CNRS INSERM U1081, 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; Institut de Recherche sur le Cancer et Vieillissement UMR7284 CNRS INSERM U1081, Université Côte d’Azur, Nice, FranceDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyImmunoallergology Unit, Careggi University Hospital, Florence, ItalyNephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, ItalyNephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, ItalyNephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 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; Institut de Recherche sur le Cancer et Vieillissement UMR7284 CNRS INSERM U1081, Université Côte d’Azur, Nice, FranceIntroduction: Rituximab is a first-line treatment for primary membranous nephropathy (pMN), with proven efficacy and safety. The use of monoclonal antibodies such as rituximab can lead to the formation of antidrug antibodies that may interfere with the therapeutic response. In pMN, anti-rituximab antibodies (ARAs) have been shown to neutralize the cytotoxicity of rituximab, thereby increasing the risk of relapse of nephrotic syndrome. However, the kinetics of ARAs over time and the effect of ARA titer on prognosis are unclear. Methods: This retrospective international multicenter study included 74 patients with pMN treated with rituximab. Here we aimed to clarify the correlation between ARAs and clinical outcome, as well as to evaluate the most appropriate timing of ARA detection. Results: Overall, 35 out of 74 patients (47%) developed ARAs after a median of 9 (interquartile range: 6–12) months following rituximab administration. ARA monitoring at month-9, month-12 and before rituximab readministration identified 88% of patients with ARAs. Clinical remission rate at 6 and 12 months after rituximab administration was significantly lower in patients with ARAs (31% vs. 56%, P = 0.03 and 54% vs. 87%, P = 0.0017, respectively). ARAs were associated with a significantly higher rate of relapse (63% vs. 29%, P = 0.036) and a higher rate of B-cell reconstitution at 6 months (74.2% vs. 50%, P = 0.048). Notably, relapse occurred earlier in patients with ARAs (22 months vs. 32 months, P = 0.01). Conclusion: The development of ARAs represents one of the most important prognostic factors in pMN, being significantly associated with a reduced remission rate and a higher relapse rate after rituximab therapy. Alternative therapies with obinutuzumab or ofatumumab should be considered for these patients.http://www.sciencedirect.com/science/article/pii/S2468024925002840antidrug antibodyanti-rituximab antibodyimmunogenicitymembranous nephropathyneutralizing antibodiesrituximab |
| spellingShingle | Marco Allinovi Maxime Teisseyre Matteo Accinno Cecilia Finocchi Vincent L.M. Esnault Marion Cremoni Tommaso Mazzierli Daniela Lazzarini Micaela Anna Casiraghi Céline Fernandez Kévin Zorzi Vesna Brglez Lorenzo Cosmi Andrea Matucci Leonardo Caroti Giulia Antognoli Calogero Lino Cirami Alessandra Vultaggio Barbara Seitz-Polski Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy Kidney International Reports antidrug antibody anti-rituximab antibody immunogenicity membranous nephropathy neutralizing antibodies rituximab |
| title | Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy |
| title_full | Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy |
| title_fullStr | Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy |
| title_full_unstemmed | Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy |
| title_short | Anti-Rituximab Antibodies Occurrence and Clinical Outcomes in Patients With Primary Membranous Nephropathy |
| title_sort | anti rituximab antibodies occurrence and clinical outcomes in patients with primary membranous nephropathy |
| topic | antidrug antibody anti-rituximab antibody immunogenicity membranous nephropathy neutralizing antibodies rituximab |
| url | http://www.sciencedirect.com/science/article/pii/S2468024925002840 |
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