Targeting B Cells Upfront: Comparing safety and efficacy of Rituximab and Corticosteroids as a first line therapy in newly diagnosed cases of adult onset minimal change disease (B-RiPP study)

Minimal change disease (MCD) accounts for approximately 15–20% of adult nephrotic syndrome (NS) cases. While corticosteroids remain the standard first-line therapy, prolonged use is associated with significant adverse effects, and relapses are common. Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown promise in frequently relapsing or steroid-dependent NS. We evaluated the efficacy and safety of RTX compared with standard corticosteroid therapy in adult-onset MCD.

In this 24-week observational study, biopsy-proven MCD patients were enrolled to receive  RTX (1 g × 2 doses, 15 days apart), or  received oral prednisolone (1 mg/kg/day for up to 8 weeks, tapered to 5–7.5 mg/day after remission). The primary endpoint was the proportion achieving complete remission (CR) within 12 weeks. Secondary endpoints included time to remission, partial remission rates, relapse rates (proteinuria >3.0 g/day or UPCR >3.0 g/g) and adverse events at 24 weeks.

A total of 72 patients were included in the analysis, comprising 35 patients in the RTX group and 37 patients in the steroid group. The baseline demographic and clinical characteristics were comparable between the two groups (figure 1). The mean age of the study population was 41.2 ± 12.4 years, with 44 (61%) being male. The mean serum creatinine at presentation was 1.29  mg/dL, and the median baseline proteinuria was 10 g/day, with no statistically significant differences between groups. At 12 weeks, complete remission (CR) was achieved in 30 of 35 patients (86%) in the RTX group and 34 of 37 patients (92%) in the steroid group (P = 0.16). Additionally, two patients (6%) in the RTX arm and two patients (5%) in the steroid arm achieved partial remission (PR) at 12 weeks, with no significant intergroup difference (P = 0.09). In the RTX group, three patients remained resistant to treatment at 12 weeks. By 24 weeks, the proportion of patients achieving CR increased to 91% in the RTX group, which remained statistically comparable to the steroid group. Rituximab induced complete depletion of peripheral CD19-positive B cells in 100% of patients, sustained for at least six months following infusion. Two patients in Ritux group relapsed after attaining remission after 12 weeks  of therapy. In terms of safety, the RTX group exhibited a more favorable adverse event profile. No clinically significant adverse events were observed in RTX-treated patients. In contrast, five patients (13%) in the steroid group developed cushingoid features, and other minor steroid-related toxicities were more frequent (P = 0.05). No cases of serious infections, infusion reactions, or treatment-related hospitalizations were reported in either group. Overall, RTX demonstrated comparable efficacy to steroids in inducing remission but was associated with fewer adverse events suggesting its potential as an effective and safer first line therapy in adult-onset MCD.

Table 1. Baseline Characteristics of the Study Population

RTX demonstrated comparable efficacy to corticosteroids in inducing remission in adult-onset MCD while offering a more favorable safety profile. Given the reduced incidence of steroid-related toxicity RTX represents a viable alternative as a first line agent to conventional steroid therapy. However, long-term data on relapse rates, maintenance therapy strategies, and cost-effectiveness are warranted before establishing RTX as a first-line agent.