Mok C C, Tse S M, Chan K L, Ho L Y
Department of Medicine, 36658 Tuen Mun Hospital , Hong Kong, SAR China.
Lupus. 2018 Apr;27(5):722-727. doi: 10.1177/0961203317739129. Epub 2017 Oct 31.
Objectives The aim of this study was to study the relationship between immunosuppressive drug treatment and survival in patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled four or more American College of Rheumatology criteria for SLE were followed longitudinally. Clinical characteristics, use of immunosuppressive agents and mortality were reviewed. Cox regression was used to study the relationship between immunosuppressive treatment and survival, adjusted for age, sex, vascular risk factors, organ damage, the anti-phospholipid antibodies and a propensity score for the indication of individual immunosuppressive agent derived from separate regression models. Results A total of 803 SLE patients were studied (92% women; age of SLE onset 33.2±14 years; follow-up time 10.8±7.7 years). The frequencies of ever use of immunosuppressive agents were: high-dose prednisolone (≥0.6 mg/kg/day for ≥4 weeks) (85%), azathioprine (63%), cyclophosphamide (25%), mycophenolate mofetil (27%), the calcineurin inhibitors (23%) and hydroxychloroquine (69%). Ninety-seven patients (12%) died and 56 (7%) patients were lost to follow-up. The causes of death were infection (44%), cerebrovascular events (12%), cardiovascular events (10%) and malignancy (8.2%). Cox regression revealed that the ever use of high-dose prednisolone, mycophenolate mofetil, calcineurin inhibitors or cyclophosphamide was not significantly associated with improved survival. However, the ever use of hydroxychloroquine (hazard ratio 0.59 (0.37-0.93); P=0.02) and azathioprine (hazard ratio 0.46 (0.28-0.75); P=0.002) was significantly associated with reduced mortality (41% and 54%, respectively) after adjustment for the propensity score and other confounding factors. A similar beneficial effect of hydroxychloroquine and azathioprine on survival was also observed in patients with lupus nephritis. Conclusions In this longitudinal cohort of Chinese SLE patients, the ever use of hydroxychloroquine and azathioprine was significantly associated with a probability of better survival. Treatment with high-dose prednisolone, cyclophosphamide, mycophenolate mofetil or the calcineurin inhibitors was not associated with long-term survival benefit.
目的 本研究旨在探讨系统性红斑狼疮（SLE）患者免疫抑制药物治疗与生存之间的关系。方法 对符合美国风湿病学会四项或更多SLE标准的患者进行纵向随访。回顾临床特征、免疫抑制剂的使用情况及死亡率。采用Cox回归分析免疫抑制治疗与生存之间的关系，并对年龄、性别、血管危险因素、器官损害、抗磷脂抗体以及根据单独回归模型得出的个体免疫抑制剂使用倾向评分进行校正。结果 共研究了803例SLE患者（92%为女性；SLE发病年龄33.2±14岁；随访时间10.8±7.7年）。免疫抑制剂的使用频率分别为：高剂量泼尼松龙（≥0.6mg/kg/天，持续≥4周）（85%）、硫唑嘌呤（63%）、环磷酰胺（25%）、霉酚酸酯（27%）、钙调神经磷酸酶抑制剂（23%）和羟氯喹（69%）。97例患者（12%）死亡，56例患者（7%）失访。死亡原因包括感染（44%）、脑血管事件（12%）、心血管事件（10%）和恶性肿瘤（8.2%）。Cox回归分析显示，使用高剂量泼尼松龙（≥0.6mg/kg/天，持续≥4周）、霉酚酸酯、钙调神经磷酸酶抑制剂或环磷酰胺与生存率提高无显著相关性。然而，校正倾向评分和其他混杂因素后，使用羟氯喹（风险比0.59（0.37-0.93）；P=0.02）和硫唑嘌呤（风险比0.46（0.28-0.75）；P=0.002）与死亡率降低显著相关（分别降低41%和54%）。在狼疮性肾炎患者中也观察到羟氯喹和硫唑嘌呤对生存具有类似的有益作用。结论 在这个中国SLE患者纵向队列中，使用羟氯喹和硫唑嘌呤与更好的生存概率显著相关。高剂量泼尼松龙、环磷酰胺、霉酚酸酯或钙调神经磷酸酶抑制剂治疗与长期生存获益无关。
