B cell depletion with rituximab in children with steroid-sensitive nephrotic syndrome: does depletion duration change outcome?

Rituximab (RTX) is widely used to prevent relapses in steroid-dependent or frequently-relapsing nephrotic syndrome (SD/FRNS). However, the impact of B-cell depletion duration on long-term outcomes remains uncertain. We compared short-term B-cell depletion (limited RTX course) with prolonged depletion maintained by repeated RTX infusions and assessed long-term disease activity.

In this retrospective multicenter study, we included children with SD/FRNS who received RTX before the age of 18 years between 2007 and 2017. Short-depletion corresponded to one or two RTX infusions, whereas prolonged-depletion reflected repeated infusions over time to maintain B-cell depletion. Prolonged remission was defined as the absence of relapse and immunosuppressive therapy for at least 2 years after the last anti-CD20 infusion.

A total of 117 patients were included (median age at first RTX infusion: 11.6 years; 65% were boys), of whom 48 (41%) had short-depletion and 69 (59%) had prolonged-depletion. Baseline characteristics were comparable between groups. At 2 years after the last RTX infusion, 69% of patients in the short-depletion group and 65% in the prolonged-depletion group were in prolonged remission. Overall, 89 patients (75%) relapsed during follow-up. Median time to first relapse was significantly longer in the long-depletion group (36 vs. 19 months, p = 0.04). Prolonged hypogammaglobulinemia was more frequent with prolonged-depletion, whereas infection rates were similar between groups.

RTX exerts a suspensive rather than curative effect in SD/FRNS. Prolonged B-cell depletion extends relapse-free survival but is associated with more frequent hypogammaglobulinemia, without an increase in severe infections.