Long-term efficacy and safety of common steroid-sparing agents in idiopathic nephrotic children

Background Calcineurin inhibitors (CNI), mycophenolate mofetil (MMF), and levamisole are common treatment choices for patients with frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS). Methods In this retrospective cohort study, we analyzed the relative efficacy and safety of tacrolimus, MMF, and levamisole over a period of 30 months, in treating 340 children with idiopathic FRNS/SDNS. The children received either MMF 1200 mg/m 2 daily, or levamisole 2.5 mg/kg on alternate days, or tacrolimus 0.1-0.2 mg/kg daily along with tapering doses of alternate-day prednisolone. Results Tacrolimus was associated with a higher rate of 30-month relapse-free survival when compared to MMF (61.7 vs. 38.5 %, p < 0.001), or levamisole (61.7 vs. 24 %, p < 0.001). However, relapse rate increased almost threefold once tacrolimus was stopped, resulting in a higher relapse rate per patient-year when compared to the MMF group (2.0 vs. 1.5, p = 0.013). The cumulative prednisolone dose per patient during the last year of the study period was also increased among tacrolimus group in comparison with MMF group (96.4 vs. 74.4 mg/kg/year, p = 0.004). Independent of the impact of drug choice, the relapse risk was higher in patients with steroid dependency at baseline (HR 2.14, 95 % CI 1.79-2.96, p < 0.0001). In comparison with few minor adverse events in other two cohorts, several serious adverse events were documented in the tacrolimus group. Conclusions Although there are serious safety concerns regarding tacrolimus, it is more effective than MMF or levamisole in maintaining relapse-free survival. However, unlike MMF, the relative efficacy of tacrolimus in preventing further relapses is seen only when the patient is on the drug. Taking together the long-term efficacy and safety data observed, MMF appears as a safe and effective alternative to tacrolimus in managing pediatric FRNS/ SDNS.