Discontinuation of mycophenolate mofetil as maintenance therapy after rituximab treatment in childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome

Mycophenolate mofetil (MMF) as maintenance therapy after rituximab treatment is effective in preventing relapses in children with complicated frequently relapsing or steroid-dependent nephrotic syndrome. However, once sustained remission has been achieved by MMF, the outcomes and risk of relapse after discontinuing MMF remain unclear.

We conducted a two-center, retrospective study of patients with childhood-onset frequently relapsing or steroid-dependent nephrotic syndrome who discontinued MMF because of sustained remission for ≥ 2 years on maintenance MMF after rituximab treatment. Relapse, additional treatment, and risk factors for relapses after MMF discontinuation were analyzed.

Sixty patients were enrolled. After tapering or discontinuation of MMF, 35 (58%) patients relapsed, and the median time from tapering to relapse was 276 days. The 50% relapse-free survival was 1.5 years using the Kaplan–Meier method. After relapses, 30 (86%) patients required reinitiation of immunosuppressants or additional rituximab treatment. The history of initial steroid-resistant nephrotic syndrome, relapses < 10 times before the first rituximab treatment with immunosuppressants, and a longer period between the last B-cell recovery and tapering MMF were significantly associated with a lower risk of relapse in a multivariate analysis using the Cox proportional hazards model (all p < 0.05).

Discontinuation of MMF may be considered in selected patients with sustained remission after rituximab treatment, particularly those with identified low-risk factors for relapse. The timing of discontinuation should be individualized according to these factors and patient-specific considerations because resumption of immunosuppressants or additional rituximab treatment is frequently required after relapse following MMF discontinuation.

A higher resolution version of the Graphical abstract is available as Supplementary information.