Maintenance therapy with mycophenolate mofetil for children with severe lupus nephritis after low-dose intravenous cyclophosphamide regimen

Abstract

Although recent studies on adults with lupus nephritis indicate that mycophenolate mofetil (MMF) may be effective in maintaining remission for patients who previously received short-term intravenous cyclophosphamide (IVCY) induction therapy, the experience with the new immunosuppressive agent in children with severe lupus nephritis has not been as satisfactory thus far. To assess the efficacy and safety of maintenance therapy with MMF, we prospectively analyzed four patients with biopsy-proven severe lupus nephritis (three girls, one boy; mean age 12 years; two with class IIIA, two with class IVG(A); mean duration of lupus nephritis 7 months) receiving MMF for at least 6 months after induction treatment. These patients had been treated previously with 6 months of low-dose IVCY combined with oral mizoribine and steroids for induction, followed by therapy with MMF adjusted to maintain predose mycophenolic acid (C0-MPA) levels at 2-5 mcg/ml. Mean follow-up after staring MMF was 27.5 months (range 6-41). The mean MMF dose required was 405 +/- 49 mg/m(2) per 12 h, which maintained mean C0-MPA levels of 3.3 +/- 0.41 mcg/ml. No patient experienced renal flares during maintenance therapy with MMF, which permitted a significant reduction in mean prednisolone dose from 11.9 +/- 1.3 to 3.9 +/- 2.6 mg/day (P = 0.003). No significant gastrointestinal or hematologic side effects of MMF were noted. This preliminary study demonstrates that maintenance therapy with MMF after a low-dose IVCY regimen appears to be a promising intervention without adverse effects in children with severe lupus nephritis. These data should be confirmed by a prospective randomized multicenter clinical trial.

Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis

“…However, in our experience by slowly increasing the dose, this main side‐effect can be avoided, although if side‐effects occur, then the total daily dose may be divided into three or four. Maintenance MMF therapy has been advocated in children with SLE and LN after induction therapies with low dose intravenous cyclophosphamide (52).…”

The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis

“…This may be the result of poor compliance of children and adolescents, which may be partially related to adverse gastrointestinal effects of MMF. On the other hand, Fujinaga et al [40] demonstrated that maintenance therapy with MMF appeared satisfactory without flares and adverse effects during follow-up in four children with severe LN. Pecoraro et al [41] reported 14 children with LN who were treated with MMF.…”

Experience with Mycophenolate Mofetil as Maintenance Therapy in five Pediatric Patients with Severe Systemic Lupus Erythematosus

“…Thereby MMF reduces B-cell proliferation, antibody synthesis and cytotoxic T-cells [23] . There is very little data on the use of MMF in children with lupus nephritis [8,17,18] , the drug is considered off label for this indication in pediatric patients. Against the background of the eff ective use of MMF in maintenance therapy in adults we hypothesized that the drug is similarly eff ective in children and adolescents with SLE.…”