Prolonged improvement of childhood onset systemic lupus erythematosus following systematic administration of rituximab and cyclophosphamide

Background: Although the combination of cyclophosphamide and rituximab has been utilized in case reports, there are no previous reports of the long term outcome of SLE treated systematically with this regimen. We report a pilot study to evaluate the efficacy of a systematically administered course of rituximab and cyclophosphamide over an eighteen month period to provide sustained improvement in childhood onset systemic lupus erythematosus (SLE). Findings: Twelve patients with childhood onset lupus nephritis or corticosteroid resistant SLE received systematic treatment with a combination of rituximab (750 mg/M-2 up to 1 gram) and cyclophosphamide (750 mg/M-2: no patient exceeded 1.8 M-2). Two administrations of rituximab and cyclophosphamide, two weeks apart, were administered at the start of study, six months later, and eighteen months later. Clinical data were collected and analyzed after sixty months of follow up. There was sustained improvement in all clinical parameters with a dramatic reduction in both mean SLEDAI score (10.1 to 1 at one year and 0 at five years p<0.005) and mean daily prednisone dosage (29.7 mg/day to 12.7 by one year and 7.0 mg/day at five years p<0.005), with sustained improvement in mean C3 (55.5 mg/ml to 113 at one year and 107.5 at five years p<0.001) which was maintained through sixty months of follow up. Serum immunoglobulin levels were transiently depressed but mean values were within the normal range for both IgG and IgM at one and five years. Few complications were observed (two episodes of febrile neutropenia during the first year of treatment were the only serious adverse events) and patients routinely reported sustained wellbeing. Conclusions: This pilot study demonstrates that a systematically administered course of rituximab and cyclophosphamide over an eighteen month period provided sustained relief for patients with childhood onset SLE which was maintained over a sixty month period, while minimizing the need for corticosteroids, without excessive toxicity.