Combination therapy of rituximab and mycophenolate mofetil in childhood lupus nephritis

Abstract

Background: In clinical trials, the addition of rituximab (RTX) to the combination therapeutic regimen of mycophenolate mofetil (MMF) and corticosteroids failed to improve outcome in lupus nephritis (LN). However, recent data suggest that RTX may have steroid-sparing beneficial effects with an efficacy similar to that of conventional regimens. We report our experience with RTX in the treatment of children with LN.

Methods: Patients treated with RTX for first occurrence of LN class III to V were enrolled in the study. Treatment consisted of methylprednisolone pulse (500 mg/m²) followed by RTX (1000 mg/1.73 m²) at days 1 and 15, and MMF (1200 mg/m²/day). Prednisolone tapering and withdrawal was left to the physician's discretion. Complete remission (CR) was defined as a urine protein-to-creatinine ratio (U Pr/Cr) of <5 mg/mg and normal serum creatinine, and partial remission (PR) as a U Pr/Cr of <30 mg/mg and a <15% rise in serum creatinine over baseline.

Results: Twelve patients were included in the study, with median follow-up of 23.7 [interquartile range (IQR) 12.8-33.5] months. Median age of the patients was 13.6 [12.3-15.1] years, median proteinuria was 32 [19-67] mg/mg and median estimated glomerular filtration rate was 76.1 [59.3-97.7] mL/min/1.73 m². Median CD20 depletion duration was 10 [6.8-11.0] months. Prednisolone was rapidly tapered, with median dose of 0.3 [0.15-0.41], 0.10 [0.09-0.16] and 0.0 [0.0-0.04] mg/kg/day at 3, 6 and 12 months respectively. At 3 months, three and seven patients achieved CR and PR, respectively; at 6 and 12 months all patients achieved remission (9 CR, 3 PR) and none relapsed during follow-up. Five infectious complications were observed, including three varicella-zoster virus (VZV) infections.

Conclusions: In our pediatric patients with LN, therapy with RTX + MMF combined with a rapid decrease in steroid appears to have been an efficacious treatment for severe LN but was associated with high rate of VZV infection. The potential of RTX to allow complete steroid avoidance warrants further investigation in children.

Keywords: Children; Lupus nephritis; Rituximab; Steroid minimization.