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Combination therapy with Rituximab and Cyclophosphamide in two girls with refractory lupus nephritis

INTRODUCTION: Despite an increasing armamentarium of immunosuppressive agents, there is still a significant morbidity and mortality associated with childhood- onset systemic lupus nephritis. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of tretment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accured over the years. Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and, more recently, rituximab. MATERIALS AND METHODS: Two female patients, 12 and 13 years old at the beginning of treatment, with active lupus nephritis that were resistant to standard immunosuppressive agents (corticosteroids and mycophenolate mofetill), were treated with Rituximab (R) 700mg/m2 (max 1g) and ciclophosphamide (C) 750mg/ m2, during the 12 months period, according to experimental protocol for class IV glomerulonephritis in patients with SLE. Patients had three cycles of R+C administered two times in two week period. First cycle was at the beginning of treatment. After that followed the four months induction therapy with C administred every one month, after which followed second cycle of R+C. Third cycle of R+C followed after six months. Clorpheniramin, paracetamol and methylprednisolone were given prior to rituximab administration, and before and after cyclophosphamide administration we used ondansteron and mesna. Both patients underwent complete clinical investigation including kidney biopsy before, during and after treatment. Global disease activity measure scores were obtained at the time of each visit, as measured by the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM). RESULTS: Prior to treatment one patient had Class IV active LN, and other class IIIa. After the treatment one patient had class IIIc, and another class V, subsequently. We also recorded decrease in values of disease activity measures, for both patients. Prior to treatment one patient had ECLAM 10.5, SLEDAI 39 and SLAM 13. After the treatment all the scores were 0. Another patient prior to treatment had ECLAM 11, SLEDAI 41 and SLAM 14. After the treatmen ECLAM was 0, 5, SLEDAI was 4 and SLAM was 1. No serious side effects or effects on growth and development were recorded. DISCUSION: Before the treatment our two patients had very active kidney disease with lower values of GF, proteinuria, immune complex deposition, crescents, endocapilar proliferation, etc. After the combined treatment active disease was converted to chronicity, with almost no activity, either in kidney or serology. REFERENCES: 1. Marks SD, Tullus K. Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis. Acta Paediatr. 2010 Mar 11. [Epub ahead of print] 2. Marks SD, Patey S, Brogan PA, Hasson N, Pilkington C, Woo P, Tullus K. B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus. Arthritis Rheum. 2005 Oct ; 52(10):3168-74.

Lupus nephritis ; rituximab ; cyclophosphamide

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