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