Heusele Marion, Clerson Pierre, Guery Benoit, Lambert Marc, Launay David, Lefevre Guillaume, Morell-Dubois Sandrine, Maillard Hélène, Le Gouellec Noémie, Hatron Pierre-Yves, Hachulla Eric
National Reference Centre for Systemic Autoimmune Diseases, Department of Internal Medicine, Claude Huriez Hospital, Université de Lille Nord-de-France, Lille, France.
Clin Rheumatol. 2014 Jun;33(6):799-805. doi: 10.1007/s10067-014-2509-2. Epub 2014 Feb 2.
The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case-control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded). Sixty-nine patients with SAID received a total of 87 RTX courses. Thirteen SIEs were reported in 12 patients leading to death in 5 patients. Patients with a history of SIE were significantly older (63.6±18.8 vs 48.8±16.7; p=0.0091), suffered most frequently of diabetes mellitus (33.3% vs 5.3%, p=0.015), had a lower CD19 count (1.0±1.2/mm3 vs 3.9±7.2/mm3) and had most frequently a prednisone dose>15 mg/day (91.7% vs 47.7%) at the start of the first RTX course. The SIE rate was 18.7 per 100 patient-years. At the initiation of the RTX course, risk factors for SIEs were lower IgG levels (OR=0.87, 95%CI=0.77-0.99, p=0.03), lower CD19 count (OR=0.85, 95%CI=0.73-1.00) and creatinine clearance≤45 ml/min (OR=7.78, 95%CI=1.36-44.38, p=0.002). Conversely history of pneumococcal vaccination significantly decreased the risk of SIEs (OR=0.11, 95%CI=0.03-0.41, p=0.0009). Concomitant treatment with prednisone at a dose>15 mg/day significantly increased the SIE risk (OR=8.07, 95%CI=1.94-33.59, p=0.0004). SIEs are frequent in SAID treated with RTX, particularly in patients receiving high-dose corticosteroids, in patients with renal insufficiency and in patients with low IgG levels or a low CD19 count.
在用于治疗严重和难治性系统性自身免疫性疾病（SAID）的利妥昔单抗（RTX）疗程后，严重细菌性感染事件（SIEs）的风险是众所周知的。SIEs的风险因素值得研究。在这项病例对照研究中，数据收集于一个内科中心，纳入了2005年至2011年间所有因SAID接受利妥昔单抗（RTX）治疗的患者（排除类风湿关节炎患者）。69例SAID患者共接受了87个RTX疗程。12例患者报告了13起SIEs，其中5例导致死亡。有SIE病史的患者年龄显著更大（63.6±18.8岁 vs 48.8±16.7岁；p = 0.0091），最常患糖尿病（33.3% vs 5.3%，p = 0.015），CD19计数较低（1.0±1.2/mm³ vs 3.9±7.2/mm³），并且在首个RTX疗程开始时最常使用泼尼松剂量>15mg/天（91.7% vs 47.7%）。SIEs发生率为每100患者年18.7例。在RTX疗程开始时，SIEs的风险因素包括较低的IgG水平（OR = 0.87，95%CI = 0.77 - 0.99，p = 0.03）、较低的CD19计数（OR = 0.85，95%CI = 0.73 - 1.00）以及肌酐清除率≤45ml/min（OR = 7.78，95%CI = 1.36 - 44.38，p = 0.002）。相反，肺炎球菌疫苗接种史显著降低了SIEs的风险（OR = 0.11，95%CI = 0.03 - 0.41，p = 0.0009）。与泼尼松剂量>15mg/天同时治疗显著增加了SIEs风险（OR = 8.07，95%CI = 1.94 - 33.59，p = 0.0004）。在接受RTX治疗的SAID中，SIEs很常见，特别是在接受高剂量皮质类固醇治疗的患者、肾功能不全患者以及IgG水平低或CD19计数低的患者中。
