【摘要】 目的 探讨原发性干燥综合征(primary Sj9gren’s Syndrome, pSS)患者发生恶性肿瘤死亡的风险。方法 纳入2016年5月至2022年1月在国家风湿病数据中心(Chinese Rheumatism Data Center, CRDC)注册登记、符合pSS 2002年欧美共识小组分类标准或2016年美国风湿病学会/欧洲风湿病联盟分类标准的pSS患者8932例的pSS患者，对临床资料(包括基本人口统计学特征、病程、临床表现、自身免疫抗体、血清补体水平和欧洲风湿病学会干燥综合征疾病活动指数(ESSDAI)评分等指标)进行随访分析，评估因实体肿瘤或血液系统肿瘤导致死亡的风险及风险影响因素。结果 共纳入8 932例pSS患者，中位随访时间为48.0(32.1,72.0)月。随访期间56例患者发生恶性肿瘤并死亡，粗肿瘤死亡率为0.6%,标准化死亡比(SMR)为0.841(95%CI:0.636～1.093),标准化肿瘤死亡率为0.5%。46例(82.1%)患者因实体肿瘤死亡，10例(17.9%)因血液系统肿瘤死亡。发生恶性肿瘤死亡的危险因素包括年龄增加(SHR=1.056,95%CI:1.028～1.085,P<0.001)、血小板计数减少(SHR=3.982,95%CI:2.123～7.471,P<0.001)、ESSDAI评分中肺高活动度(SHR=5.291,95%CI:1.827～15.328,P=0.002)。免疫抑制治疗治疗为保护因素(SHR=0.348,95%CI:0.164～0.741,P=0.006)。首位实体肿瘤死因为肺癌，共16例，占恶性肿瘤比例为28.6%,粗肺癌死亡率为0.2%,SMR 1.284(95%CI:0.734～2.085),标准化肿瘤死亡率为0.2%。发生肺癌死亡的危险因素包括男性(HR=8.356,95%CI:2.676～26.100,P<0.001)、年龄增加(HR=1.102,95%CI:1.053～1.153,P<0.001)、ESSDAI评分高度肺活动性(2 vs. 0分：HR=7.041,95%CI:2.233～22.208,P=0.001,3 vs. 0分：HR=17.349,95%CI:3.593～83.764,P<0.001)。羟氯喹治疗为其保护因素(HR=0.213,95%CI:0.069～0.663,P=0.008)。结论 pSS患者因恶性肿瘤死亡的风险与普通人群无明显差异。发生恶性肿瘤死亡事件的危险因素包括高龄、血小板计数减少、ESSDAI评分中肺高度活动性；免疫抑制治疗可以降低总体肿瘤死亡风险。肺癌死亡的危险因素为男性、年龄增加、ESSDAI评分中肺高活动度，羟氯喹降低肺癌死亡风险。更多还原

【Abstract】 Objective To investigate the risk of mortality due to malignancy in patients with primarySj?gren’s Syndrome(pSS).Methods From May 2016 to January 2022, patients registered in the ChineseRheumatism Data Center(CRDC) who fulfilled the 2002 American-European Consensus Group or the 2016 A-merican College of Rheumatology∕European League Against Rheumatism classification criteria for pSS were en-rolled. Clinical data, including basic demographic features, disease duration, clinical manifestations, au-toantibodies, serum complement levels, and EULAR Sj?gren’s Syndrome Disease Activity Index(ESSDAI),were analyzed retrospectively to assess the risk and influencing factors of death due to solid tumors or hematolog-ic malignancies.Results The median follow-up duration for the 8, 932 pSS patients was 48. 0(32. 1, 72. 0)months. During this period, 56 patients died due to malignant tumors, with a crude tumor mortality rate of0. 6%. The standardized mortality ratio( SMR) was 0. 841, 95% CI: 0. 636-1. 093, with a standardizedtumor mortality rate of 0. 5%. Among these, 46 patients( 82. 1%) died due to solid tumors, and 10(17. 9%) due to hematologic malignancies. Factors associated with an increased risk of death due to malignanttumors included aging(SHR = 1. 056, 95% CI: 1. 028-1. 085,P< 0. 001), thrombocytopenia( SHR =3. 982, 95% CI: 2. 123-7. 471,P<0. 001), and high pulmonary activity based on ESSDAI scores(SHR =5. 291, 95% CI: 1. 827-15. 328,P= 0. 002). Immunosuppressive therapy was identified as a protectivefactor(SHR = 0. 348, 95% CI: 0. 164-0. 741,P= 0. 006). Lung cancer(16, 28. 6%) was the leadingcause of death in solid tumors. The crude mortality rate of lung cancer was 0. 2%, with an SMR of 1. 284,95% CI: 0. 734-2. 085, and a standardized tumor mortality rate of 0. 2%. Risk factors for death due to lungcancer included male gender(HR = 8. 356, 95% CI: 2. 676-26. 100,P< 0. 001), aging(HR = 1. 102,95% CI: 1. 053-1. 153,P< 0. 001), and high pulmonary activity lesions in the ESSDAI score(2vs. 0points: HR =7. 041, 95% CI: 2. 233-22. 208,P=0. 001; 3vs. 0 points: HR = 17. 349, 95% CI: 3. 593-83. 764,P< 0. 001). Hydroxychloroquine was a protective factor(HR = 0. 213, 95% CI: 0. 069-0. 663,P= 0. 008).Conclusion The risk of death due to malignant tumors in pSS patients does not significantly dif-fer from the general population. Aging, thrombocytopenia, and high pulmonary activity based on ESSDAI scoresare risk factors for malignant tumor-related death events. Immunosuppressive therapy can decrease the overall riskof tumor-related mortality. Risk factors for death due to lung cancer include male, aging, and high pulmonary ac-tivity based on the ESSDAI score, while hydroxychloroquine reduces the risk of death due to lung cancer.更多还原