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

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.