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Combination therapy of rituximab and mycophenolate mofetil in childhood lupus nephritis

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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.

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Authors and Affiliations

  1. Pediatric Nephrology Department, Robert Debré Hospital, Assistance publique–Hôpitaux de Paris (APHP), Paris, France

    Julien Hogan, Véronique Baudouin, Theresa Kwon, Georges Deschênes & Olivier Niel

  2. Pediatric Nephrology Unit, Pellegrin-Enfants Hospital–Bordeaux University, Bordeaux, France

    Astrid Godron & Jérôme Harambat

Authors
  1. Julien Hogan
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  2. Astrid Godron
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  3. Véronique Baudouin
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  4. Theresa Kwon
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  5. Jérôme Harambat
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  6. Georges Deschênes
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  7. Olivier Niel
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Corresponding author

Correspondence to Julien Hogan.

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The study protocol was approved by the Ethics committees of the participating institutions.

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Hogan, J., Godron, A., Baudouin, V. et al. Combination therapy of rituximab and mycophenolate mofetil in childhood lupus nephritis. Pediatr Nephrol 33, 111–116 (2018). https://doi.org/10.1007/s00467-017-3767-4

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  • DOI: https://doi.org/10.1007/s00467-017-3767-4

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