基于多状态马尔科夫模型预估系统性红斑狼疮患者器官受损进展及影响因素

doi:10.16352/j.issn.1001-6325.2025.06.0800

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (6): 800-806.doi: 10.16352/j.issn.1001-6325.2025.06.0800

基于多状态马尔科夫模型预估系统性红斑狼疮患者器官受损进展及影响因素

李路¹, 李良明¹, 余兵¹, 李梦涛^2*, 王艳红^1*

1.中国医学科学院基础医学研究所北京协和医学院基础学院流行病与卫生统计学系,北京 100005;
2.中国医学科学院北京协和医学院北京协和医院风湿免疫科,国家皮肤与免疫疾病临床医学研究中心(NCRC-DID),疑难重症及罕见病国家重点实验室,风湿免疫病学教育部重点实验室,北京 100730

收稿日期:2025-02-26 修回日期:2025-03-21 出版日期:2025-06-05 发布日期:2025-05-26
通讯作者: ^*mengtaomengtao.li@cstar.org.cn;wyhong826@pumc.edu.cn
基金资助:
中国医学科学院医学与健康科技创新工程 (2019-I2M-2-008)

A multi-state Markov model study to estimate organ damage progression and influencing factors in systemic lupus erythematosus patients

LI Lu¹, LI Liangming¹, YU Bing¹, LI Mengtao^2*, WANG Yanhong^1*

1. Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005;
2. Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID), State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Peking Union Medical College Hospital, CAMS & PUMC,Beijing 100730, China

Received:2025-02-26 Revised:2025-03-21 Online:2025-06-05 Published:2025-05-26

摘要/Abstract

摘要： 目的构建多状态马尔科夫模型探讨中国系统性红斑狼疮(SLE)患者器官损伤累积的动态模式,探索不同疾病阶段器官损伤进展的可能影响因素,为优化临床治疗策略和卫生经济学评价提供依据。方法利用中国系统性红斑狼疮研究协作组多中心注册队列(CSTAR)中满足本研究纳入标准的SLE患者作为研究对象。基于系统性红斑狼疮国际合作组/美国风湿病学会损伤指数(SDI)将SLE划分五个不可逆状态(SDI=0、1、2、≥3及死亡),分别用S0,S1,S2,S3和Death表示。利用SLE患者不同时点的诊疗数据,利用R语言“mstate”包构建多状态马尔科夫模型。结果本研究纳入23 926例SLE患者,累计随访122 030次。基线SLE患者中20 892例患者无任何器官损伤,在随访期间内,不同器官损伤累积状态下的转移概率分别为7.01%(S0→S1), 12.58%(S1→S2), 10.64%(S2→S3)和12.19%(S3→Death)。多状态模型显示:年龄、性别、病程、平均疾病活动性指数(SLEDAI)评分、激素使用剂量、重要脏器受累情况均与器官损伤状态转移相关。不同状态间转移时年龄每增1岁,SLE患者器官损伤累积风险增加2-3%(P＜0.01);神经系统受累(S0→S1:HR=1.34;S1→S2:HR=1.53;S2→S3:HR=1.73)、心肺系统受累(S0→S1:HR=3.66;S1→S2:HR=1.51;S2→S3:HR=1.52)、肾脏受累(S0→S1:HR=1.24)和血液系统受累(S0→S1:HR=1.24)可能会加速器官损伤累积。结论 SLE患者器官损伤累积的转移概率随着时间的推移逐渐增高,在疾病早期阶段尽可能减少重要脏器的受累,不同治疗阶段需动态调整治疗策略。

关键词: 系统性红斑狼疮, 多状态马尔科夫模型, 转移概率

Abstract: Objective To establish a multi-state Markov model of systemic lupus erythematosus(SLE) for patients in China and to explore the transition rule of organ damage accumulation and possible factors affecting the transition between states. Methods A retrospective cohort study was conducted using the data from CSTAR. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index(SDI) was divided into five irreversible disease states(SDI=0, 1, 2, ≥3, and death, marked as S0, S1, S2, S3, Death). The R “mstate” package was used for statistical analysis. Results This study included 23 926 cases of SLE patients with cumulative follow-up of 12 030 visits. Among these patients, 21 070 patients had no any organ damage at baseline. At the follow-up period, the transition probabilities of organ damage of S0→S1, S1→S2, S2→S3, S3→Death were 7.01%, 12.58%, 10.64%, and 12.19%, respectively. The multi-state Markov model showed that age, gender, disease duration, SLEDAI score, corticosteroid dosage, and involvement of major organs were associated with the transition of organ damage status, each 1 year increased was associated with a 2%~3% increase in risk of damage accumulation risk(P＜0.01). Also, neurological(S0→S1:HR=1.34;S1→S2:HR=1.53;S2→S3:HR=1.73), cardiopulmonary(S0→S1:HR=3.66;S1→S2:HR=1.51;S2→S3:HR=1.52), renal(S0→S1:HR=1.24)and hematological involvement(S0→S1:HR=1.24)might be the risk factors. Conclusions The probability of organ damage accumulation in SLE patients increases over time. Therefore, in the early stage of the disease, the involvement of important organs needs to be minimized and the treatment strategy should be dynamically adjusted at different stages of treatment.

Key words: systemic lupus erythematosus, multi-state Markov model, transition probability

中图分类号:

李路, 李良明, 余兵, 李梦涛, 王艳红. 基于多状态马尔科夫模型预估系统性红斑狼疮患者器官受损进展及影响因素[J]. 基础医学与临床, 2025, 45(6): 800-806.

LI Lu, LI Liangming, YU Bing, LI Mengtao, WANG Yanhong. A multi-state Markov model study to estimate organ damage progression and influencing factors in systemic lupus erythematosus patients[J]. Basic & Clinical Medicine, 2025, 45(6): 800-806.

参考文献 15

[1]	Fava A, Petri M. Systemic lupus erythematosus: Diagnosis and clinical management[J]. J Autoimmun, 2019, 96: 1-13.
[2]	Mak A, Isenberg D A, Lau CS. Global trends, potential mechanisms and early detection of organ damage in SLE[J]. Nat Rev Rheumatol, 2013, 9: 301-310.
[3]	Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the systemic lupus international collaborating clinics American College of Rheumatology damage index for systemic lupus erythematosus[J]. Arthritis Rheum, 1996, 39: 363-369.
[4]	Taraborelli M, Cavazzana I, Martinazzi N, et al. Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years[J]. Lupus, 2017, 26: 1197-1204.
[5]	Jonsen A, Bengtsson AA, Hjalte F, et al. Total cost and cost predictors in systemic lupus erythematosus-8-years follow-up of a Swedish inception cohort[J]. Lupus, 2015, 24: 1248-1256.
[6]	Thomas G, Mancini J, Jourde-Chiche N, et al. Mortality associated with systemic lupus erythematosus in France assessed by multiple-cause-of-death analysis[J]. Arthritis Rheumatol, 2014, 66: 2503-2511.
[7]	Yee CS, Su L, Toescu V, et al. Birmingham SLE cohort: outcomes of a large inception cohort followed for up to 21 years[J]. Rheumatology, 2015, 54: 836-843.
[8]	Urowitz MB, Gladman DD, Ibañez D, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort[J]. Arthritis Care Res(Hoboken), 2012, 64: 132-137.
[9]	Segura BT, Bernstein BS, Mcdonnell T, et al. Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort[J]. Rheumatology(Oxford), 2020, 59: 524-533.
[10]	Sánchez E, Gómez LM, Lopez-Nevot MA, et al. Evid-ence of association of macrophage migration inhibitory factor gene polymorphisms with systemic lupus erythematosus[J]. Genes Immun, 2006, 7: 433-436.
[11]	Foote A, Briganti EM, Kipen Y, et al. Macrophage migration inhibitory factor in systemic lupus erythematosus[J]. J Rheumatol, 2004, 31: 268-273.
[12]	Akhavan PS, Su J, Lou W, et al. The early protective effect of hydroxychloroquine on the risk of cumulative damage in patients with systemic lupus erythematosus[J]. J Rheumatol, 2013, 40: 831-841.
[13]	Fei Y, Zhao L, Wu L, et al. Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal(PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China[J]. Ann Rheum Dis, 2025, 84: 274-283.
[14]	Kandane-Rathnayake R, Kent JR, Louthrenoo W, et al. Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus[J]. Lupus, 2019, 28: 1669-1677.
[15]	Sutton EJ, Davidson JE, Bruce IN. The systemic lupus international collaborating clinics(SLICC) damage index: a systematic literature review[J]. Semin Arthritis Rheum, 2013, 43: 352-361.

基于多状态马尔科夫模型预估系统性红斑狼疮患者器官受损进展及影响因素

A multi-state Markov model study to estimate organ damage progression and influencing factors in systemic lupus erythematosus patients

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