A prospective cohort study of rituximab in the treatment of refractory nephrotic syndrome

Objective To explore the efficacy and safety of rituximab (RTX) in the treatment of autoimmune nephropathy manifested as refractory nephrotic syndrome (RNS). Methods A single-center prospective cohort study was conducted on RNS patients treated with RTX between March 2017 and December 2019. The subjects were divided into the primary nephropathy (PN) group and the secondary nephropathy (SN) group. Based on the estimated glomerular filtration rate (eGFR) before RTX treatment, the SN group was then divided into the SN-1 group (eGFR ≥ 30 ml/min) and the SN-2 group (eGFR < 30 ml/min). Biochemical parameters and clinical data were recorded during follow-up. Results Fifty-four patients were followed up for at least 6 months. The overall remission rates were 65%, 66.7%, 27.3% in the PN, SN-1, and SN-2 groups, respectively (P = 0.022). Kaplan–Meier analysis showed a significant difference of the renal survival among the three subgroups (P < 0.001). Multivariate Cox regression analysis showed that eGFR value before treatment was an independent predictor (HR 0.919, 95%CI 0.863–0.979) for renal survival. In terms of adverse events, infection accounted for 56.6%. The incidence of severe infection was 10%, 25% and 50% in PN group, SN-1 group and SN-2 group, respectively. Conclusions RTX may be a promising option in RNS patients with eGFR ≥ 30 ml/min/1.73m2. However, it has little effect on prognosis in patients with secondary RNS with eGFR < 30 ml/min/1.73m2, but with a high risk of severe infection.

All-case Japanese post-marketing surveillance of the real-world safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome

Background Rituximab is conditionally approved in Japan for use in patients with refractory nephrotic syndrome. To meet the conditions of approval, an all-case post-marketing surveillance study was conducted to confirm the real-world safety and efficacy of rituximab in patients of all ages with refractory nephrotic syndrome. Methods All patients scheduled to receive rituximab treatment for refractory nephrotic syndrome were eligible to register (registration: August 29, 2014 through April 15, 2016); the planned observation period was 2 years from the initiation of rituximab treatment (intravenous infusion, 375 mg/m2 once weekly for four doses). The study was conducted at 227 hospitals throughout Japan. Adverse drug reactions (ADRs) were collected for safety outcomes. The efficacy outcomes were relapse-free period and the degree of growth in pediatric (< 15 years) patients. Results In total, 997 (447 pediatric) patients were registered; 981 (445) were included in the safety analysis set; 852 (402) completed the 2-year observation period; and 810 (429) were included in the efficacy analysis set. Refractory nephrotic syndrome had developed in childhood for 85.0% of patients, and 54.6% were aged ≥15 years. ADRs were observed in 527 (53.7%) patients, treatment-related infection/infestation in 235 (24.0%) patients, and infusion reactions in 313 (31.9%) patients. The relapse-free period was 580 days (95% confidence interval, 511–664). There was a significant change in height standard deviation score (pediatric patients; mean change, 0.093; standard deviation, 0.637; P = 0.009). Conclusion The safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome were confirmed in the real-world setting. Clinical trial registration UMIN000014997.