Single (375 mg/m) vs. double dose of rituximab along with mycophenolate mofetil for children with steroid-dependent/frequently relapsing nephrotic syndrome: a multicentre open-label randomized controlled trial.

Background: Optimal dosing of rituximab when given with mycophenolate mofetil (MMF) for frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS) remains uncertain.

Methods: This was a prospective, non-inferiority, open-label randomized controlled multicentre study. Children (2-18 years old) with difficult FRNS/SDNS were randomized to group A (rituximab 375 mg/m once) or group B (rituximab 375 mg/m twice; 7-14 days apart) followed by continuous MMF and 3 months of tapered steroids. Primary outcome at an 18-month follow-up was time to first relapse. Secondary outcomes included post rituximab time to CD19 repopulation, sustained remission and significant adverse events (SAEs).

Results: Ninety-six children (median age 8.6 years; IQR 6.4 to 11.3 years, 72% male) were randomized, 48 per arm. CD19 depletion (< 1%) was achieved in both groups. Three from single dose and two from double dose arm were lost to follow-up or withdrew. After 18 months, although non-inferiority could not be demonstrated, there was no difference in primary outcome either by intention-to-treat or per-protocol analysis. The restricted mean time to first relapse was 14.5 months (95% CI 13.1-15.9) in group A and 14.8 months (95% CI 13.5-16.1) in group B (p = 0.69). Relapse rate was similar between group A (19/45; 42%) and group B (16/46; 35%) (p = 0.53, hazard ratio 0.86 (95% CI 0.46-1.6)). Secondary outcomes were also similar between the groups.

Conclusions: Among children with FRNS/SDNS although non-inferiority could not be demonstrated, no statistically significant difference in outcome was found between 375 and 750 mg/m rituximab when accompanied with MMF.