Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

Philipp Gauckler; Anna Matyjek; Seleni Kapsia; Smaragdi Marinaki; Luis F. Quintana; Montserrat M. Diaz; Catherine King; Siân Griffin; Raja Ramachandran; Balazs Odler; Kathrin Eller; Ayşe Serra Artan; Safak Mirioglu; Martin Busch; Maxi Schaepe; Kultigin Turkmen; Chee Kay Cheung; Ruth J. Pepper; Gema Fernandez Juarez; Julio Pascual; Pilar Auñón; Clara García-Carro; Antolina Rodriguez; Federico Alberici; Leonella Luzardo; Natalia Chebotareva; Ulf Schönermarck; Loreto Fernández; Jai Radhakrishnan; Karina Guaman; Yonatan Peleg; Léa Hoisnard; Vincent Audard; Marios Papasotiriou; Nina Krnanska; Vladimir Tesar; Zdenka Hruskova; Annette Bruchfeld; Maria Stangou; Georgios Lioulios; Stanislas Faguer; David Ribes; Sofiane Salhi; Martin Windpessl; Krešimir Galešić; Matija Crnogorac; Nikola Zagorec; Gert Mayer; Andreas Kronbichler

doi:10.1681/ASN.0000000520

Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

Philipp Gauckler, Anna Matyjek, Seleni Kapsia, Smaragdi Marinaki, Luis F. Quintana, Montserrat M. Diaz, Catherine King, Siân Griffin, Raja Ramachandran, Balazs Odler, Kathrin Eller, Ayşe Serra Artan, Safak Mirioglu, Martin Busch, Maxi Schaepe, Kultigin Turkmen, Chee Kay Cheung, Ruth J. Pepper, Gema Fernandez Juarez, Julio PascualPilar Auñón, Clara García-Carro, Antolina Rodriguez, Federico Alberici, Leonella Luzardo, Natalia Chebotareva, Ulf Schönermarck, Loreto Fernández, Jai Radhakrishnan, Karina Guaman, Yonatan Peleg, Léa Hoisnard, Vincent Audard, Marios Papasotiriou, Nina Krnanska, Vladimir Tesar, Zdenka Hruskova, Annette Bruchfeld, Maria Stangou, Georgios Lioulios, Stanislas Faguer, David Ribes, Sofiane Salhi, Martin Windpessl, Krešimir Galešić, Matija Crnogorac, Nikola Zagorec, Gert Mayer, Andreas Kronbichler^*

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Background:Long-Term outcomes of rituximab-Treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown.Methods:A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-Treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months.Results:183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-To-Treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-Three of 151 (55%) initial responders achieved long-Term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-Term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching-11 (95% CI:-18 to-8) mL/min/1.73m².Conclusions:Rituximab facilitated achievement of initial and long-Term response in a majority of adult patients with difficult-To-Treat podocytopathies. Maintenance treatment with rituximab further associated with long-Term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.

Original language	English (US)
Article number	10.1681/ASN.0000000520
Journal	Journal of the American Society of Nephrology
DOIs	https://doi.org/10.1681/ASN.0000000520
State	Accepted/In press - 2024

ASJC Scopus subject areas

General Medicine

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10.1681/ASN.0000000520

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Gauckler, P., Matyjek, A., Kapsia, S., Marinaki, S., Quintana, L. F., Diaz, M. M., King, C., Griffin, S., Ramachandran, R., Odler, B., Eller, K., Artan, A. S., Mirioglu, S., Busch, M., Schaepe, M., Turkmen, K., Cheung, C. K., Pepper, R. J., Juarez, G. F., ... Kronbichler, A. (Accepted/In press). Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies. Journal of the American Society of Nephrology, Article 10.1681/ASN.0000000520. https://doi.org/10.1681/ASN.0000000520

@article{1ce1f3d12d4848cb8d72c49b82ba9c51,

title = "Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies",

abstract = "Background:Long-Term outcomes of rituximab-Treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown.Methods:A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-Treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months.Results:183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-To-Treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-Three of 151 (55%) initial responders achieved long-Term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-Term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching-11 (95% CI:-18 to-8) mL/min/1.73m2.Conclusions:Rituximab facilitated achievement of initial and long-Term response in a majority of adult patients with difficult-To-Treat podocytopathies. Maintenance treatment with rituximab further associated with long-Term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.",

author = "Philipp Gauckler and Anna Matyjek and Seleni Kapsia and Smaragdi Marinaki and Quintana, {Luis F.} and Diaz, {Montserrat M.} and Catherine King and Si{\^a}n Griffin and Raja Ramachandran and Balazs Odler and Kathrin Eller and Artan, {Ay{\c s}e Serra} and Safak Mirioglu and Martin Busch and Maxi Schaepe and Kultigin Turkmen and Cheung, {Chee Kay} and Pepper, {Ruth J.} and Juarez, {Gema Fernandez} and Julio Pascual and Pilar Au{\~n}{\'o}n and Clara Garc{\'i}a-Carro and Antolina Rodriguez and Federico Alberici and Leonella Luzardo and Natalia Chebotareva and Ulf Sch{\"o}nermarck and Loreto Fern{\'a}ndez and Jai Radhakrishnan and Karina Guaman and Yonatan Peleg and L{\'e}a Hoisnard and Vincent Audard and Marios Papasotiriou and Nina Krnanska and Vladimir Tesar and Zdenka Hruskova and Annette Bruchfeld and Maria Stangou and Georgios Lioulios and Stanislas Faguer and David Ribes and Sofiane Salhi and Martin Windpessl and Kre{\v s}imir Gale{\v s}i{\'c} and Matija Crnogorac and Nikola Zagorec and Gert Mayer and Andreas Kronbichler",

year = "2024",

doi = "10.1681/ASN.0000000520",

language = "English (US)",

journal = "Journal of the American Society of Nephrology",

issn = "1046-6673",

publisher = "Wolters Kluwer Health",

}

Gauckler, P, Matyjek, A, Kapsia, S, Marinaki, S, Quintana, LF, Diaz, MM, King, C, Griffin, S, Ramachandran, R, Odler, B, Eller, K, Artan, AS, Mirioglu, S, Busch, M, Schaepe, M, Turkmen, K, Cheung, CK, Pepper, RJ, Juarez, GF, Pascual, J, Auñón, P, García-Carro, C, Rodriguez, A, Alberici, F, Luzardo, L, Chebotareva, N, Schönermarck, U, Fernández, L, Radhakrishnan, J, Guaman, K, Peleg, Y, Hoisnard, L, Audard, V, Papasotiriou, M, Krnanska, N, Tesar, V, Hruskova, Z, Bruchfeld, A, Stangou, M, Lioulios, G, Faguer, S, Ribes, D, Salhi, S, Windpessl, M, Galešić, K, Crnogorac, M, Zagorec, N, Mayer, G & Kronbichler, A 2024, 'Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies', Journal of the American Society of Nephrology. https://doi.org/10.1681/ASN.0000000520

TY - JOUR

T1 - Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

AU - Gauckler, Philipp

AU - Matyjek, Anna

AU - Kapsia, Seleni

AU - Marinaki, Smaragdi

AU - Quintana, Luis F.

AU - Diaz, Montserrat M.

AU - King, Catherine

AU - Griffin, Siân

AU - Ramachandran, Raja

AU - Odler, Balazs

AU - Eller, Kathrin

AU - Artan, Ayşe Serra

AU - Mirioglu, Safak

AU - Busch, Martin

AU - Schaepe, Maxi

AU - Turkmen, Kultigin

AU - Cheung, Chee Kay

AU - Pepper, Ruth J.

AU - Juarez, Gema Fernandez

AU - Pascual, Julio

AU - Auñón, Pilar

AU - García-Carro, Clara

AU - Rodriguez, Antolina

AU - Alberici, Federico

AU - Luzardo, Leonella

AU - Chebotareva, Natalia

AU - Schönermarck, Ulf

AU - Fernández, Loreto

AU - Radhakrishnan, Jai

AU - Guaman, Karina

AU - Peleg, Yonatan

AU - Hoisnard, Léa

AU - Audard, Vincent

AU - Papasotiriou, Marios

AU - Krnanska, Nina

AU - Tesar, Vladimir

AU - Hruskova, Zdenka

AU - Bruchfeld, Annette

AU - Stangou, Maria

AU - Lioulios, Georgios

AU - Faguer, Stanislas

AU - Ribes, David

AU - Salhi, Sofiane

AU - Windpessl, Martin

AU - Galešić, Krešimir

AU - Crnogorac, Matija

AU - Zagorec, Nikola

AU - Mayer, Gert

AU - Kronbichler, Andreas

PY - 2024

Y1 - 2024

N2 - Background:Long-Term outcomes of rituximab-Treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown.Methods:A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-Treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months.Results:183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-To-Treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-Three of 151 (55%) initial responders achieved long-Term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-Term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching-11 (95% CI:-18 to-8) mL/min/1.73m2.Conclusions:Rituximab facilitated achievement of initial and long-Term response in a majority of adult patients with difficult-To-Treat podocytopathies. Maintenance treatment with rituximab further associated with long-Term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.

AB - Background:Long-Term outcomes of rituximab-Treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown.Methods:A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-Treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months.Results:183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-To-Treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-Three of 151 (55%) initial responders achieved long-Term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-Term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching-11 (95% CI:-18 to-8) mL/min/1.73m2.Conclusions:Rituximab facilitated achievement of initial and long-Term response in a majority of adult patients with difficult-To-Treat podocytopathies. Maintenance treatment with rituximab further associated with long-Term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.

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U2 - 10.1681/ASN.0000000520

DO - 10.1681/ASN.0000000520

M3 - Article

C2 - 39431468

AN - SCOPUS:85208564423

SN - 1046-6673

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

M1 - 10.1681/ASN.0000000520

ER -

Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

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