Tanaka Yoshiya, Yamamoto Kazuhiko, Takeuchi Tsutomu, Nishimoto Norihiro, Miyasaka Nobuyuki, Sumida Takayuki, Shima Yoshihito, Takada Kazuki, Matsumoto Isao, Saito Kazuyoshi, Koike Takao
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan.
Mod Rheumatol. 2007;17(3):191-7. doi: 10.1007/s10165-007-0565-z. Epub 2007 Jun 20.
Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus (SLE), safer and more effective therapies are prerequisite. We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and, therefore, safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial. An open-label, multicenter study of 15 patients with active and refractory SLE (total British Isles Lupus Assessment Group [BILAG] score 8 to 17) was conducted. Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week. Assessment of safety, infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks. Rituximab was well tolerated, with most experiencing no significant adverse effects. B cells rapidly reduced in all patients and remained low until 6 months post-treatment. Four patients developed human antichimeric antibodies without affecting efficacy of rituximab. Changes in routine safety laboratory tests clearly related to rituximab were not observed. Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks. Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise, at least for the majority of patients experiencing profound B-cell depletion.
尽管皮质类固醇和免疫抑制剂被广泛用于治疗系统性红斑狼疮（SLE），但更安全、更有效的疗法是必不可少的。我们和其他人已经报道，靶向B细胞的抗CD20抗体利妥昔单抗对难治性SLE有效，因此，通过一项多中心I/II期临床试验评估了利妥昔单抗在SLE中的安全性和临床疗效。对15例活动性难治性SLE患者（不列颠群岛狼疮评估组[BILAG]总分8至17分）进行了一项开放标签、多中心研究。5例SLE患者每周接受4次500mg/体的利妥昔单抗输注，10例SLE患者每隔一周接受2次1000mg/体的输注。安全性、输注反应和不良反应评估作为临床耐受性的主要结局，并在28周时进行评估。利妥昔单抗耐受性良好，大多数患者无明显不良反应。所有患者的B细胞迅速减少，并在治疗后6个月内保持较低水平。4例患者产生了人抗嵌合抗体，但未影响利妥昔单抗的疗效。未观察到与利妥昔单抗明显相关的常规安全实验室检查变化。14例可评估患者中有9例达到了BILAG评分的主要或部分临床缓解，且在28周时泼尼松龙剂量显著降低。利妥昔单抗治疗对于活动性SLE患者似乎是安全的，并且至少对于大多数经历深度B细胞耗竭的患者具有显著的治疗前景。
