Incidence and risk factors of tuberculosis in systemic lupus erythematosus patients: a multi-center prospective cohort study

Lifan Zhang; Xiaoqing Zou; Nan Jiang; Lantian Xie; Jianghao Liu; Zhengrong Yang; Qifei Cao; Chunlei Li; Xiaochuan Sun; Fengchun Zhang; Yan Zhao; Xiaofeng Zeng; Xiaochun Shi; Xiaoqing Liu; ETHERTB study team

doi:10.3389/fimmu.2023.1157157

Incidence and risk factors of tuberculosis in systemic lupus erythematosus patients: a multi-center prospective cohort study

Front Immunol. 2023 Jun 14:14:1157157. doi: 10.3389/fimmu.2023.1157157. eCollection 2023.

Authors

Lifan Zhang^{1

2

3}, Xiaoqing Zou⁴, Nan Jiang⁵, Lantian Xie⁶, Jianghao Liu⁶, Zhengrong Yang¹, Qifei Cao¹, Chunlei Li⁷, Xiaochuan Sun⁷, Fengchun Zhang⁸, Yan Zhao⁸, Xiaofeng Zeng⁸, Xiaochun Shi^{1

3}, Xiaoqing Liu^{1

2

3

4}; ETHERTB study team

Affiliations

¹ Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, China.
³ Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ 4 + 4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁶ Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
⁷ Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁸ Key Laboratory of Rheumatology & Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Ministry of Education, Beijing, China.

Abstract

Objectives: Both burdens of tuberculosis (TB) and systemic lupus erythematosus (SLE) in China are ranked as top three in the world. SLE patients are at high risk for TB, but so far, there are no guidelines for TB prevention and management targeting this population in China. This study aims to investigate the incidence of active tuberculosis (ATB) and to explore the risk factors for developing ATB in SLE patients, and to provide evidence for TB prevention and management for SLE patients in China.

Methods: A multi-center prospective cohort study was conducted. SLE patients were enrolled from clinics and wards of 13 tertiary hospitals in Eastern, Middle, and Western China from September 2014 to March 2016. Baseline demographic features, TB infection status, clinical information, and laboratory data were collected. ATB development was examined during follow-up visits. Kaplan-Meier method was applied to plot survival curves, and Log-rank test was used to evaluate differences. Cox proportional-hazards model was used to explore the risk factors for ATB development.

Results: With a median follow-up time of 58 months [interquartile range (IQR): 55-62], 16 out of 1361 SLE patients developed ATB. The 1-year incidence of ATB was 368 [95% confidence interval (CI): 46-691] per 100,000. Over a 5-year period, the cumulative incidence of ATB was 1141 [95% CI: 564-1718] per 100,000, and the incidence density was 245 per 100,000 person-years. Cox regression models were constructed with maximum daily dose of glucocorticoids (GCs) as a continuous variable and a categorical variable, respectively. In model 1, maximum daily dose of GCs (pills per day) [adjusted hazard ratio (aHR)=1.16, 95%CI: 1.04-1.30, p=0.010] and TB infection (aHR=8.52, 95%CI: 3.17-22.92, p<0.001) were independent risk factors for ATB development. In model 2, maximum daily dose of GCs≥30 mg/d (aHR =4.81, 95%CI: 1.09-22.21, P=0.038) and TB infection (aHR=8.55, 95%CI: 3.18-23.00, p<0.001] were independent risk factors for ATB development.

Conclusions: SLE patients had a higher incidence of ATB compared to the general population. The risk of developing ATB was even higher with increased daily dose of GCs or in a status of TB infection, in which case TB preventive treatment should be considered.

Keywords: cohort study; epidemiology; risk facors; systemic lupus erythematosus; tuberculosis.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Glucocorticoids
Humans
Incidence
Latent Tuberculosis*
Lupus Erythematosus, Systemic* / complications
Lupus Erythematosus, Systemic* / drug therapy
Lupus Erythematosus, Systemic* / epidemiology
Prospective Studies
Risk Factors
Tertiary Care Centers
Tuberculosis* / epidemiology

Substances

Glucocorticoids

Grants and funding

This study was supported by the National Science and Technology Major Project of the People’s Republic of China (2014ZX10003003 and 2017ZX10201302-003) and National High Level Hospital Clinical Research Funding (2022-PUMCH-C-013 and 2022-PUMCH-A-119).