Efficacy and Safety of Tac or MMF for Children with Steroid-Sensitive but Frequent Relapse or Steroid-Dependent Nephrotic Syndrome: A Nationwide, Multicentre Randomized Study

Background: Both tacrolimus (TAC) and mycophenolate mofetil (MMF) are recommended for children with frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). However, their comparative effectiveness and safety have not been evaluated through randomized controlled studies. Methods: In this multicenter, randomized, open-label, controlled trial, 270 children aged 2-18 years with FRNS/SDNS were allocated at a 1:1 ratio to receive either TAC (0.025-0.05 mg/kg, orally twice daily) or MMF (10-15 mg/kg, orally twice daily) for one year, along with a tapering regimen of steroids. The primary endpoint was 1-year relapse-free survival. Relapse frequency, cumulative steroid dosage and safety profiles were also evaluated. The trial was prospectively registered at ClinicalTrials.gov (NCT04048161). Results: A total of 243 out of 270 patients completed the trial, and their data were analyzed and reported. Compared with MMF, TAC significantly reduced the risk of relapse by 65% (HR = 0.35, 95% CI: 0.21–0.56, P <0.0001) in the intention-to-treat analysis. This difference was also significant after adjusting for the per-protocol analysis (HR = 0.36, 95% CI: 0.22–0.58, P <0.0001). Among the relapsed patients, the median time to first relapse was 225.5 days in the TAC group and 165.5 days in the MMF group. The TAC group had fewer annual relapses (mean [SD], 0.319 [0.936] vs. 0.778 [1.274]) and a reduced cumulative dose of steroid (0.221 [0.103] vs. 0.337 [0.222] mg/kg/d) than did the MMF group. The safety profile was similar in both groups, with infections being the most common adverse event. Conclusion: In children with FRNS/SDNS, a 1-year course of TAC therapy significantly extended the period of relapse-free survival in comparison to MMF treatment. Funding: Other NIH Support - National Key R&D Program of China, 2022YFC2705103, Government Support - Non-U.S.