Tacrolimus or Mycophenolate Mofetil for Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome

Importance: Both tacrolimus (TAC) and mycophenolate mofetil (MMF) are recommended for children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). However, their comparative effectiveness and safety have not been evaluated through randomized clinical trials. Objective: To compare the effectiveness and safety of TAC and MMF in children with FRNS or SDNS. Design, Setting, and Participants: In this multicenter, open-label randomized clinical trial conducted at 12 pediatric nephrology centers across China, 270 children aged 2 to 18 years with FRNS or SDNS were allocated at a 1:1 ratio to treatment with either TAC or MMF. The study was conducted from November 2019 to July 2023, and data analysis was completed from July 2023 to March 2024. Intervention: Patients received either TAC (0.025-0.050 mg/kg, orally twice daily) or MMF (10-15 mg/kg, orally twice daily) for 1 year, along with a tapering regimen of steroids. Main Outcomes and Measures: The primary end point was 1-year relapse-free survival. Relapse frequency, cumulative steroid dosage, and safety profiles were also evaluated. Results: A total of 292 patients from 12 care centers were assessed for eligibility, and 270 patients were randomized to receive either TAC (n = 135) or MMF (n = 135). Among 270 patients, median (IQR) age was 6.91 (4.25-9.96) years, and 70 patients (25.9%) were female. Compared with MMF, the 1-year relapse-free survival rate in the TAC group was 1.86-fold higher (hazard ratio [HR], 2.86; 95% CI, 1.79-4.76; P < .001) in the intention-to-treat analysis. This difference was also significant after adjusting for the per-protocol analysis (HR, 2.78; 95% CI, 1.72-4.55; P < .001). The mean (SD) time to first relapse was significantly longer in the TAC group (323.99 [98.33] days) compared to the MMF group (263.21 [132.84] days). Furthermore, the TAC group showed a lower annual relapse rate than the MMF group (17.78% vs 41.48%) and required a significantly lower mean (SD) cumulative steroid dose (0.22 [0.10] mg/kg/day vs 0.34 [0.22] mg/kg/day). The safety profile was similar in both groups. Conclusions and Relevance: In this randomized clinical trial, compared with MMF, a 1-year course of TAC therapy significantly extended the period of relapse-free survival in children with FRNS or SDNS. Trial Registration: ClinicalTrials.gov Identifier: NCT04048161.