Olfat M, Silverman E D, Levy D M
Division of Rheumatology, Hospital for Sick Children, Canada.
Division of Rheumatology, Hospital for Sick Children, Canada University of Toronto, Canada.
Lupus. 2015 Aug;24(9):966-72. doi: 10.1177/0961203315578764. Epub 2015 Mar 24.
Autoimmune thrombocytopenia (AITP) and hemolytic anemia (AIHA) are common in childhood-onset systemic lupus erythematosus (cSLE) and may be refractory to conventional therapies. Our objectives were to: (a) examine our experience; (b) determine the rate and durability of response to rituximab; and (c) evaluate its safety in our cSLE population with refractory cytopenias.
We performed a single-center retrospective cohort study of cSLE patients with refractory AITP or AIHA treated with rituximab between 2003 and 2012. Outcomes included the time to complete clinical response, time to B-cell depletion, duration of response and time to flare. Adverse events were also analyzed.
Twenty-four (6%) of 394 cSLE patients received rituximab for refractory cytopenia. The indication was AITP in 16 (67%), AIHA in five (21%) and both in three (13%) patients. The median (interquartile range (IQR)) time from cytopenia onset to rituximab therapy was 16 (7-27) months for AITP and 10 (2-29) months for AIHA. Complete response following the first course of rituximab occurred at a median (IQR) of 48 (14-103) days, only one patient failed to respond. Five (21%) patients had one or more flare episodes at 22 (15-27) months. Infusion reactions were rare and one infection with herpes zoster required hospitalization in the first 12 months. Three of four patients with low IgG levels prior to the first rituximab course developed persistent hypogammaglobulinemia, and three patients have required intravenous immunoglobulin replacement.
Rituximab appears to be a well-tolerated, safe and long-lasting therapy for cSLE patients with refractory AITP and/or AIHA. Caution should be exercised when considering rituximab for patients with preexisting hypogammaglobulinemia.
自身免疫性血小板减少症（AITP）和溶血性贫血（AIHA）在儿童期系统性红斑狼疮（cSLE）中很常见，并且可能对传统疗法难治。我们的目的是：（a）审视我们的经验；（b）确定对利妥昔单抗反应的发生率和持久性；以及（c）评估其在我们患有难治性血细胞减少症的cSLE患者群体中的安全性。
我们对2003年至2012年间接受利妥昔单抗治疗的难治性AITP或AIHA的cSLE患者进行了一项单中心回顾性队列研究。结果包括达到完全临床反应的时间、B细胞耗竭的时间、反应持续时间和复发时间。还分析了不良事件。
394例cSLE患者中有24例（6%）因难治性血细胞减少症接受了利妥昔单抗治疗。适应证为AITP的有16例（67%），AIHA的有5例（21%），两者皆有的有3例（13%）。AITP从血细胞减少症发作到利妥昔单抗治疗的中位（四分位间距（IQR））时间为16（7 - 27）个月，AIHA为10（2 - 29）个月。利妥昔单抗第一疗程后的完全缓解发生的中位（IQR）时间为48（14 - 103）天，只有1例患者无反应。5例（21%）患者在22（15 - 27）个月时有1次或更多次复发。输注反应罕见，在最初12个月内有1例带状疱疹感染需要住院治疗。在首次利妥昔单抗疗程前IgG水平低的4例患者中有3例出现持续性低丙种球蛋白血症，3例患者需要静脉注射免疫球蛋白替代治疗。
对于患有难治性AITP和/或AIHA的cSLE患者，利妥昔单抗似乎是一种耐受性良好、安全且持久的疗法。对于已有低丙种球蛋白血症的患者考虑使用利妥昔单抗时应谨慎。
