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

Abstract

BackgroundAlthough 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).FindingsTwelve patients with childhood onset lupus nephritis or corticosteroid resistant SLE received systematic treatment with a combination of rituximab (750 mg/M2 up to 1 gram) and cyclophosphamide (750 mg/M2: no patient exceeded 1.8 M2). 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.ConclusionsThis 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.

Cyclophosphamide Administration Routine in Autoimmune Rheumatic Diseases: A Review

“…11 In children, cyclophosphamide may be used in the treatment of nephrotic syndrome and systemic lupus erythematosus. 12,13 Cyclophosphamide can be administered by oral or intravenous route. 14 The intravenous administration is more frequent in the field of rheumatology, taking into account studies showing an efficacy similar to that of oral treatment, but with less toxicity, for example, a decrease in premature ovarian failure, less severe infection, and lower overall exposure of the urinary tract to acrolein, a toxic metabolite of cyclophosphamide.…”

Experience in Rituximab Administration in Children with Systemic Lupus Erythematosus: a Retrospective Study of the Case Series

“…на фоне применения ритук-симаба у детей с СКВ была аналогична таковой для традиционных схем [18]. В нашем исследовании отме-чалось более заметное снижение дозы кортикостерои-дов (с 0,88 до 0,17 мг/кг в сут и с 33,75 до 10,0 мг/сут за время наблюдения), чем в исследовании L. В двух исследованиях с относительно большими выборками пациентов с ювенильной формой СКВ наи-более значимые изменения были отмечены для таких параметров, как СОЭ, уровень гемоглобина, глобальная врачебная оценка заболевания и уровни компонентов комплемента [16,17].…”

“…[17] изменения значений индек-са BILAG на фоне применения ритуксимаба отмечено не было, тогда как в исследовании T. J. Lehman и соавт. выявлено значимое снижение значений индекса SLEDAI [18]. В исследовании G. Moroni и соавт.…”

“…В США ритуксимаб разрешен к применению у пациентов с АНЦА-ассоциированными васкулитами в возрасте старше 15 лет [15]. В немного-численных исследованиях по применению препарата при СКВ у детей показано снижение курсовой дозы систем-ных кортикостероидов, а также снижение активности заболевания при относительной безопасности лечения [16][17][18]. Однако в этих исследованиях не применялись современные индексы оценки активности СКВ у детей, что не позволяет дать более точную оценку динамики активности СКВ на фоне терапии ритуксимбом.…”

Lúpus Eritematoso Cutâneo: Manifestações Clínicas E Análise Laboratorial

“…A terapia combinada com rituximab e ciclofosfamida resultaram em redução significativa na média de prednisona dosagem, a taxa de sedimentação de eritrócitos (LEHMAN et al, 2014). Em 2000, a literatura inclui inúmeras séries e meta-análise de apoio à célula B terapia de esgotamento, incluindo uma revisão sistemática de 188 portadores de doença grave, refratária mostrando 91% tinha melhoria significativa em pelo menos uma manifestação lúpus (BELMONT, 2013).…”