RITUXIMAB MAINTENANCE THERAPY IS EFFECTIVE IN MAINTAINING REMISSION IN STEROID DEPENDENT AND FREQUENT RELAPSING ADULT NEPHROTIC SYNDROME

Introduction:

While minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) have variable degree of steroid responsiveness, a substantial number of patients become steroid dependent (SD) or frequent relapsing (FR). Prolonged exposure to corticosteroids is associated with a considerable toxicity and should therefore be avoided. Rituximab, an anti CD-20 antibody, is a promising steroid sparing agent, however there are no randomized controlled trial in adults to evaluate its effectiveness and treatment protocol in SD/FR nephrotic syndrome (NS). We aimed to evaluate the efficacy of Rituximab in adults with SD/FR NS and to examine the impact of maintenance therapy.

Methods:

A retrospective single center cohort study, evaluating patients with SD/FR NS treated with Rituximab. Rituximab was given at induction, most commonly at two doses of 1,000mg each. Supplementary maintenance doses were subjected to the treating nephrologist decision. Primary outcome was number of relapses and time to first relapse. Time to first relapse was additionally measured using Cox Regression survival analysis for differences between administration of maintenance doses (maintenance vs. no-maintenance). Safety was evaluated.

Results:

Twenty-one adults were included; median age 54.6 years, 52.4% were females. Fourteen patients (66.6%) were diagnosed with MCD, 5 (23.8%) with FSGS and 2 cases were considered as steroid sensitive NS due to inability to perform a biopsy. Median follow up time was 39.6 months. Number of relapses decreased significantly after Rituximab treatment (median relapses 0 after compared to 3 before treatment, W = 3.70, p<.001). Time to first relapse was significantly shorter prior to Rituximab therapy compared to after treatment (median 11 vs. 536 days, respectively, W = 3.05, p=.002). Fourteen patients received repeated Rituximab doses, in five patients the second course was following a relapse, and nine received prophylactic maintenance dose. Median total dose of Rituximab was 3000 mg (IQR: 2000-4750 mg), administered over a median of 3 courses (IQR: 1.0-4.0 courses). Hazzard Ratio (HR) for relapse was higher in patients who received one Rituximab course compared to those who received additional maintenance therapy (HR = 4.31, 95% CI: 1.13-16.39, p = 0.032, figure 1). Treatment was generally well-tolerated, serious adverse events included hospitalization due to cholecystitis one week after first Rituximab dose and severe COVID-19 two months after treatment.

Conclusions:

Rituximab emerges as an efficient safe steroid sparing in patients with SD/FR NS. Additional maintenance dose given while patients maintained remission achieved significantly longer remission. Further studies are required for better precision of treatment protocol to ensure maximal efficacy with minimal side effects.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.