Combination therapy of rituximab and mycophenolate mofetil in childhood lupus nephritis
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.
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.
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.
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.
KeywordsLupus nephritis Children Rituximab Steroid minimization
- 1.Mackie FE, Kainer G, Adib N, Boros C, Elliott EJ, Fahy R, Munro J, Murray K, Rosenberg A, Wainstein B, Ziegler JB, Singh-Grewal D (2015) The national incidence and clinical picture of SLE in children in Australia—a report from the Australian Paediatric surveillance unit. Lupus 24:66–73CrossRefPubMedGoogle Scholar
- 9.Alsufyani KA, Ortiz-Alvarez O, Cabral DA, Tucker LB, Petty RE, Nadel H, Malleson PN (2005) Bone mineral density in children and adolescents with systemic lupus erythematosus, juvenile dermatomyositis, and systemic vasculitis: relationship to disease duration, cumulative corticosteroid dose, calcium intake, and exercise. J Rheumatol 32:729–733PubMedGoogle Scholar
- 13.Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G (2012) Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study. Arthritis Rheum 64:1215–1226CrossRefPubMedGoogle Scholar
- 16.Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L (2013) Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 72:1280–1286CrossRefPubMedGoogle Scholar
- 18.Ruggiero B, Vivarelli M, Gianviti A, Benetti E, Peruzzi L, Barbano G, Corona F, Ventura G, Pecoraro C, Murer L, Ghiggeri GM, Pennesi M, Edefonti A, Coppo R, Emma F (2013) Lupus nephritis in children and adolescents: results of the Italian collaborative study. Nephrol Dial Transplant 28:1487–1496CrossRefPubMedGoogle Scholar
- 19.Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dorner T, Doria A, Ferrario F, Floege J, Houssiau FA, Ioannidis JP, Isenberg DA, Kallenberg CG, Lightstone L, Marks SD, Martini A, Moroni G, Neumann I, Praga M, Schneider M, Starra A, Tesar V, Vasconcelos C, van Vollenhoven RF, Zakharova H, Haubitz M, Gordon C, Jayne D, Boumpas DT (2012) Joint European league against rheumatism and European renal association-European dialysis and transplant association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 71:1771–1782CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Nikpour M, Urowitz MB, Ibanez D, Harvey PJ, Gladman DD (2011) Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proof-of-concept cohort study. Arthritis Res Ther 13:R156CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Okamoto A, Abe A, Okamoto M, Kobayashi T, Inaguma Y, Tokuda M, Yanada M, Morishima S, Kanie T, Yamamoto Y, Tsuzuki M, Mizuta S, Akatsuka Y, Yatsuya H, Yoshikawa T, Emi N (2014) A varicella outbreak in B-cell lymphoma patients receiving rituximab-containing chemotherapy. J Infect Chemother 20:774–777CrossRefPubMedGoogle Scholar