Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome

Childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS) is a chronic condition often requiring long-term, high-dose steroid therapy, which carries significant side effects. While rituximab is a standard treatment, most patients relapse once peripheral B cells recover. This study investigated whether adding mycophenolate mofetil (MMF) as a maintenance therapy after rituximab could sustain remission and prevent treatment failure.

This multicenter, randomized, double-blind, placebo-controlled trial enrolled 78 children with complicated FRNS/SDNS. All participants received a standard course of rituximab. They were then randomized to receive either MMF or a placebo for 17 months. The primary outcome was the time to treatment failure, defined as the development of frequent relapses, steroid dependence, steroid resistance, or the need for additional immunosuppressive agents or further rituximab. The study included both the 17-month treatment period and a subsequent follow-up period.

During the active treatment period (up to day 505), MMF was highly effective: it reduced the risk of treatment failure by 80%, significantly lowered the relapse rate by 74%, and allowed for a 57% reduction in daily steroid doses compared to the placebo group. However, the protective effect was not sustained after MMF was discontinued. Many patients in the MMF group experienced relapses during the follow-up period, causing the cumulative treatment failure-free survival curves to converge with the placebo group. Consequently, the primary endpoint—measured across the entire study duration—did not reach statistical significance (P=0.07).

This trial provides strong evidence that MMF is an effective, well-tolerated maintenance strategy to bridge the period after rituximab therapy, helping children avoid the complications of prolonged steroid use. While it does not offer a permanent cure, it serves as a valuable tool for managing disease activity. The findings suggest that clinicians should consider the duration of maintenance therapy carefully, as the risk of relapse remains high once immunosuppressive support is withdrawn.