研究背景：系统性红斑狼疮(Systemic Lupus Erythematosus, SLE)是一种多脏器系统受累的自身免疫性疾病。近年来随着诊治水平的提高，SLE患者的长期预后得到 显著改善。目前，国外对于SLE的预后研究已相对较多，但是我国对于SLE患者 的预后研究目前仍处于起步阶段，尚缺乏除生存以外其他预后结局相关的研究。既 往流行病学研究表明不同种族间SLE病情及预后存在差异，与其他人种相比，亚洲 SLE患者疾病活动度更高，器官受损更重。 研究目的：通过双向队列研究探讨单中心SLE患者的长期预后，包括长期生存及相 关预后因素，预后相关中间结局（器官受损、脏器受累、复发-缓解）以及相关危险 因素，以初步反映目前中国SLE患者的预后情况，为多中心队列研究提供指示方向。 研宄方法：纳入CSTAR注册队列一期患者中北京协和医院单中心的SLE患者，入 组时收集人口学、家族史、临床表现和免疫学指标等作为基线信息。入组后按照统 一的随访方案及患者病情规律门诊随访，研究终点时查找并收集门诊随访资料，并 采用电话随访的方式补充未规律随访患者信息，并进行电话问卷调查。采用Kaplan-Meier 生存分析、COX回归分析以及LOGISTIC回归分析的方法对不同预后结局及 其相关因素进行分析。 研宄结果：单中心SLE患者整体1、 3、 5年生存率分别为99.2%， 95.9%， 94.3%,主 要死亡原因中排首位者为感染，占37.5%。 Kaplan-Meier单因素分析显示起病至确 诊时间>1年组[7.586,p< 0.001]、入组时器官受损组[9.190,p = 0.002])、入组时合并 重要脏器受累组[8.346,p=0.004]长期生存率明显下降。生存相关COX多因素回归分 析显示起病至确诊时间〉1年[HR 3.096, 95%CI 1.109-8.643， p=0.031]、入组时器官 受损[HR 6.841, 95%CI 1.890-24.752， p=0.003]、入组时重要脏器受累[HR 5.233, 95%CI 1.466-18.682， p=0.011]为独立的预后不良因素。入组时存在器官受损患者比 例为12.8%，至随访第6年累积存在器官受损患者比例增长至27.5%。新确诊患者 1、 3、 5年无器官受损率为95.9%， 90.5%， 84.1%。器官受损相关COX回归分析显 示起病年龄>50岁[RR 3.538, 95%CI 1.602-7.816， p=0.002]、入组时存在器官受损[RR 2.670, 95%CI 1.106-6.449，p=0.029]、脏器复发[RR 3.167, 95%CI 1.609-6.232，p=0.001] 为新出现器官受损的危险因素，其中起病年龄>50岁、脏器复发为其独立危险因素。 入组时脏器受累排前4位的是：HEMA 54.6% (137)， LN49.0% (123)， SERO 12.7% (32)， NPSLE9.56% (24)，随访过程中新出现脏器受累排前3位的是：LN 43.3% (13)， NPSLE23.30% (7)， HEMA 10% (3)。脏器受累相关LOGISTIC回归分析显示男性[OR 3.194, 95%CI 1.151-8.867，p=0.026]、入组时病程>3年[OR 4.420, 95%CI 2.322-8.413，p< 0.001]、抗ds-DNA( + )+低补体[OR 2.115, 95%CI 1.186-3.770，p=0.002] 为LN独立相关因素；抗ds-DNA(+)[OR 1.931, 95%CI 1.060-3.515，p=0.031]为HEMA 相关因素；抗r-RNP(+)[OR 2.658, 95%CI 1.215-5.861 ，p=0.014]为NPSLE相关因素。 患者年复发率14.7%-20.6%，患者5年无复发率为47.2%， 5年无脏器复发率为69.1%。 所有复发类型中排前5位的是：肾脏复发30.4%，皮肤黏膜复发29.5%，血液系统 复发14.1%，关节复发9.25%，神经系统复发3.52%。患者达到持续5年临床缓解 的比例为17.1%。单中心队列中未规律随诊患者占19.2%，未随诊原因主要为自觉 病情稳定36%，路途遥远48%。与规律随诊患者相比，新出现器官受损、脏器受累 无显著差异。 研究结论：单中心研究结果显示SLE患者长期生存情况已明显改善。目前感染仍为 主要死亡原因。确诊时单纯LN或HEMA的患者长期预后与无脏器受累患者相当， 而合并重要脏器受累的患者长期预后明显较差。起病至确诊年龄>1年、器官受损及 合并重要脏器受累是独立的预后不良因素。既往器官受损、起病年龄>50岁及脏器 复发为新出现器官受损的危险因素，预防脏器复发将进一步减少器官受损的出现。 新发脏器受累以LN及NPSLE为主，其中男性、病程>3年及合并低补体及抗ds-DNA(+)患者更易合并LN，出现抗r-RNP(+)患者更易合并NPSLE。我国SLE患者 年复发率较国外队列复发率高，长期缓解率低，脏器复发以肾脏、血液系统和神经 系统复发为主。其中，超过10%的复发由未规律随访或未规律服药导致，未来应关 注并加强NPSLE的治疗及复发的预防，并且加强SLE患者的教育，从而进一步降 低复发率，使更多患者能达到长期缓解状态，减少器官受损的发生，从而改善SLE 患者的长期预后。未规律随访患者多自觉病情稳定，但疾病仍然存在进展，所以定 期监测及调整治疗相当重要。因此，加强患者的疾病宣教，同时加强地方专科建设 有利于改善患者随诊情况，从而有利于患者长期预后的改善。

Objective This study aims to exhibit the prognosis, both mortality and morbidity, for patients with Systemic Lupus Erythematosus (SLE) in a large single-center and multi-center cohort in China. Methods A large multi-center cohort of Chinese SLE patients were recruited from April 2009 to February 2010, and followed up regularly in clinic. Data for baseline, follow-up and survival were collected, including demography, manifestations, activity (SLEDAI-2K), SLE International Collaborating Clinics Damage Index (SDI), and medications. Data from the largest single-center was collected and analyzed first, and then the multic-center. Kaplan-Meier method was adopted for survival analysis. Predicting and risk factors for both mortality and morbidity were evaluated by COX proportional hazard model. Associated factors were analyzed by Logistic Regression model. Results A total of 260 patients (female: male=237:23) were included in single-center cohort study. The 1, 3 and 5 year survival rates were 99.2%, 95.9% and 94.3%, respectively. Multivariate Cox regression analysis indicated that time from onset to diagnosis>1 year[HR 3.096, 95%CI 1.109-8.643, p=0.031], organ damage[HR 6.841, 95%CI 1.890-24.752, p=0.003] and severe organ involvement[HR 5.233, 95%CI 1.466-18.682,p=0.011] are independent predictors for all-cause mortality. The proporation of patients with organ damage increased from 12.8% at baseline to 27.5% at year 6. The top 3 organ damages were musculoskeletal 32.1%, neuropsychiatric 17.9% and pulmonary 10.7%. Cox regression analysis indicated that onset age>50[RR 3.538, 95%CI 1.602-7.816, p=0.002], previous organ damage[RR 2.670, 95%CI 1.106-6.449, p=0.029] and organ involved flare[RR3.167, 95%CI 1.609-6.232, p=0.001] are risk factors for new damage, and among them late-onset age and organ involved flare are independent risk factors for new damage. At entry, the top 2 involved organs were HEMA 54.6% and LN 49.0%. For new developed organ involvement, LN (43.3%) and NPSLE (23.3%) took the most part. The yearly flare rate for consecutively followed up patients was 14.7-20.6%. The rate with no flare at year 1, 3 and 5 were 79.3%, 59.8%, 47.2%. Finally, 17.1% of the consecutively followed patients developed prolonged clinical remission (remission for 5 years). At entry, a total of 2104 SLE patients were recruited for multi -center cohort study and 1542 patients were followed up. The 1,3 and 5 year survival rates were 99.3%,98.2%, 97.2%. Multivariate Cox regression analysis indicated that male[HR 2.021, 95%CI 1.053-3.881, p=0.034], age at onset>50[HR 3.482, 95%CI 1.762-6.878, p<0.001], time from onset to diagnosis>1 year[HR 1.771, 95%CI 1.070-2.930, p=0.026] and organ damage[HR2.968, 95%CI 1.693-5.202, p<0.001], serositis[HR 2.247, 95%CI 1.083-4.665, p=0.030] and severe organ involvement[HR 2.326, 95%CI 1.191-4.543, p=0.013] are independent predictors for all-cause mortality. Conclusion Long-term survival rates in our cohort are comparable to previous reported ones for both Chinese and Caucasians. For Chinese SLE patients, gender, late-onset age, time from onset to diagnosis, organ damage, serositis and severe organ involvement are prognostic factors and deserve more attention in the future. Late-onset age, previous Damage and organ involved flare may lead to more damage accrual afterwards for Chinese SLE patients.