B cell depletion as a novel treatment for systemic lupus erythematosus - A phase I/II dose-escalation trial of rituximab
B cell depletion as a novel treatment for systemic lupus erythematosus - A phase I/II dose-escalation trial of rituximab
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DOI：
10.1002/art.20430
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发表时间：
2004-08-01
影响因子：
--
通讯作者：
Sanz, I
中科院分区：
文献类型：
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作者：
Looney, RJ;Anolik, JH;Sanz, I
目标。需要更安全、更有效的治疗系统性红斑狼疮（SLE）的方法。B淋巴细胞已被证明在SLE中起着根本的致病作用，因此，使用利妥昔单抗消除B细胞可能是SLE的一种新的治疗方法。一项I/II期剂量递增试验将利妥昔单抗添加到正在进行的SLE治疗中。利妥昔单抗分为单次输注100 mg/m(2)（低剂量）、单次输注375 mg/m(2)（中剂量）或4次输注（间隔1周）375 mg/m(2)（高剂量）。检测CD19+淋巴细胞以确定B细胞清除的有效性。系统性狼疮活动测量（SLAM）评分作为临床疗效的主要指标。利妥昔单抗在该患者群体中耐受性良好，大多数患者没有明显的不良反应。仅有3例严重不良事件被认为与使用利妥昔单抗无关。大多数患者（17例中有11例）存在严重的B细胞衰竭
Objective. Safer and more effective therapies are needed for the treatment of systemic lupus erythematosus (SLE). B lymphocytes have been shown to play fundamental pathogenic roles in SLE, and therefore, elimination of B cells with the use of rituximab may represent a new therapy for SLE.Methods. A phase I/II dose-escalation trial of rituximab added to ongoing therapy in SLE was conducted. Rituximab was administered as a single infusion of 100 mg/m(2) (low dose), a single infusion of 375 mg/m(2) (intermediate dose), or as 4 infusions (1 week apart) of 375 mg/m(2) (high dose). CD19+ lymphocytes were measured to determine the effectiveness of B cell depletion. The Systemic Lupus Activity Measure (SLAM) score was used as the primary outcome for clinical efficacy.Results. Rituximab was well tolerated in this patient population, with most experiencing no significant adverse effects. Only 3 serious adverse events, which were thought to be unrelated to rituximab administration, were noted. A majority of patients (11 of 17) had profound B cell depletion (to