No Difference in Time to Relapse Between Two Non-Steroid Immunosuppressants in Childhood Nephrotic Syndrome: JAMA

Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to variation in worldwide practice.

Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity.

A study was done to evaluate the comparative effectiveness of cyclophosphamide vs calcineurin inhibitors (tacrolimus or cyclosporine) for childhood nephrotic syndrome relapse prevention. Using target trial emulation methods, the study team emulated a pragmatic, open-label clinical trial using available data from the Insight Into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics (INSIGHT) study. INSIGHT is a multicenter, prospective cohort study in the Greater Toronto Area, Canada. Participants included children (1 to 18 years) with steroid-sensitive nephrotic syndrome diagnosed between 1996 and 2019 from the Greater Toronto Area, who initiated cyclophosphamide or a calcineurin inhibitor treatment. Data analysis was performed in 2024.

The primary outcome was time to relapse, analysed by weighted Kaplan-Meier and Cox proportional hazards models. Secondary outcomes included relapse rates, subsequent immunosuppression, kidney function, hypertension, adverse events, and quality of life. Results Of 578 children, 131 initiated calcineurin inhibitors, and 87 sequentially initiated both medications. Baseline characteristics were well balanced after propensity score weighting. During the median 5.5-year follow-up, there was no significant difference in time to relapse between calcineurin inhibitor vs cyclophosphamide treatment.

Relapses were more common after calcineurin inhibitor treatment than cyclophosphamide in the weighted cohorts, but not statistically significant. There were also no significant differences in subsequent relapse rates, nonsteroid immunosuppression use, or kidney function between medications. Calcineurin inhibitor treatment was associated with more hospitalisations and intravenous albumin use. In this study, there was no evidence of a difference in time to relapse after cyclophosphamide and calcineurin inhibitor treatment in children with nephrotic syndrome. Cyclophosphamide treatment is shorter in duration and more accessible globally than calcineurin inhibitors.

Reference:

Robinson CH, Aman N, Banh T, et al. Comparative Efficacy of Nonsteroid Immunosuppressive Medications in Childhood Nephrotic Syndrome. JAMA Pediatr. Published online January 27, 2025. doi:10.1001/jamapediatrics.2024.5286