Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies
Authors: 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
Journal: Journal of the American Society of Nephrology (2024)

Key Points Fifty-five percent of patients achieve long-term remission after rituximab treatment. This is influenced by maintenance therapy with rituximab. A substantial reduction of annualized relapse rate and concomitant immunosuppression was observed after rituximab treatment. Background Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or FSGS) 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 One hundred eighty-three adult patients ( n =64 with FSGS 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 3 years. Maintenance therapy with rituximab was associated with a better relapse-free survival (hazard ratio, 2.05; 95% confidence interval [CI], 1.07 to 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 with 36% of patients without maintenance treatment (odds ratio, 2.69; 95% CI, 1.27 to 5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI, 1.0 to 1.7) before to 0.17 (95% CI, 0.00 to 0.24) relapses per year after rituximab initiation. Over the 36 months of follow-up, a stable course of eGFR was observed in those who initially responded with either complete or partial remission, whereas nonresponders experienced a reduction in eGFR reaching −11 (95% CI, −18 to −8) ml/min per 1.73 m 2 . 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 was further associated with long-term relapse-free survival over 3 years. Nonresponse to initial rituximab treatment was associated with poor kidney prognosis.