Hickman R A, Hira-Kazal R, Yee C-S, Toescu V, Gordon Caroline
Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Clin Rheumatol. 2015 Feb;34(2):263-71. doi: 10.1007/s10067-014-2839-0. Epub 2015 Jan 8.
In contrast to randomised clinical trials, open-label studies have suggested that B cell depletion by a course of rituximab is associated with a significant clinical benefit. Our aim was to assess the safety and efficacy of rituximab in 15 refractory lupus patients, particularly those with more than one course of therapy. Disease activity was measured by the classic British Isles Lupus Assessment Group (BILAG) index, anti-DNA antibodies and complement levels. We assessed immunoglobulin levels, functional antibodies and serious adverse events. The mean patient age ± SD was 37.9 ± 7.2 years and mean disease duration was 8.5 ± 3.3 years; 46% were Afro-Caribbean, 27% South Asian, 20% Caucasian and 7% others. Twelve patients responded by 6 months; six avoided major flare for >1 year. Complete absence of disease activity (BILAG D/E) lasted for 5.5 (SD 3.8) months and 4.8 (SD 3.6) months after the first (n = 15) and second (n = 9) rituximab course, respectively. The mean 6-month reduction in daily prednisolone was 10.4 (SD 11.4) mg/day and 10.7 (SD 9.3) mg/day from baseline after the first and second course, respectively. Patients with low C3/C4 normalised their C3 by 6 months. Most patients with raised anti-dsDNA normalised after rituximab courses. Serious adverse events only occurred after more than four courses of rituximab. Rituximab was safe and efficacious for treating patients with refractory systemic lupus erythematosus (SLE) and was associated with significant steroid reduction, but more than four courses of rituximab was associated with an increased risk of serious infection in two patients.
与随机临床试验不同，开放标签研究表明，利妥昔单抗疗程导致的B细胞耗竭与显著的临床获益相关。我们的目的是评估利妥昔单抗在15例难治性狼疮患者中的安全性和有效性，尤其是那些接受过不止一个疗程治疗的患者。通过经典的英伦三岛狼疮评估组（BILAG）指数、抗DNA抗体和补体水平来衡量疾病活动度。我们评估了免疫球蛋白水平、功能性抗体和严重不良事件。患者的平均年龄±标准差为37.9±7.2岁，平均病程为8.5±3.3年；46%为非洲加勒比裔，27%为南亚裔，20%为白种人，7%为其他种族。12例患者在6个月时出现反应；6例患者在超过1年的时间里避免了严重发作。在首次（n = 15）和第二次（n = 9）利妥昔单抗疗程后，疾病活动完全消失（BILAG D/E）分别持续了5.5（标准差3.8）个月和4.8（标准差3.6）个月。从基线开始，首次和第二次疗程后，每日泼尼松龙在6个月时的平均减少量分别为10.4（标准差11.4）mg/天和10.7（标准差9.3）mg/天。C3/C4低的患者在6个月时C3恢复正常。大多数抗双链DNA升高的患者在利妥昔单抗疗程后恢复正常。严重不良事件仅在接受超过四个疗程的利妥昔单抗后出现。利妥昔单抗治疗难治性系统性红斑狼疮（SLE）患者安全有效，且与显著减少类固醇使用相关，但超过四个疗程的利妥昔单抗与两名患者严重感染风险增加相关。
