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

• DOI: 10.1681/asn.0000000520
• Publication Date: 2024-10-16T16:20:02Z
• 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 Ju...; 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

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 m2.

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.