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/m2 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.