Time-Dependent Mortality Predictors in Primary Sjögren’s Syndrome: C-Reactive Protein for Early Risk and Age for Late Outcomes

Jia-Qi Chen,1,2 Yan Zhang,1,2 Zi-Wei Huang,1,2 Jian-Ying Yang,3 Jia-He Liao,1,2 Chun-Xin Lei,1,2 Xi-Ya Zhang,1,2 Xin-Bo Yu,1,2 Tzu-Hua Wu,1,2 Zi-Han Liu,1,2 Bo-Jie Tang,1,2 Xuan-Yi Zhou,1,2 Tian-Tian Deng,1,2 Jing Luo,2,* Wei-Jiang Song,4 Qing-Wen Tao2,* 1Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Traditional Chinese Medicine Department of Rheumatism, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Graduate School, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Traditional Chinese Medicine Department, Peking University Third Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Luo, Traditional Chinese Medicine Department of Rheumatism, China-Japan Friendship Hospital, No. 2 Yinghua Dongjie, Chaoyang District, Beijing, 100029, People’s Republic of China, Email [email protected] Qing-Wen Tao, Traditional Chinese Medicine Department of Rheumatism, China-Japan Friendship Hospital, No. 2 Yinghua Dongjie, Chaoyang District, Beijing, 100029, People’s Republic of China, Email [email protected]: To identify risk factors for near-term and long-term death in patients with primary Sjogren’s syndrome (pSS).Patients and Methods: This ambispective cohort study included all patients with pSS treated at China–Japan Friendship Hospital between 2013 and 2023. The time-dependent Cox regression analysis was used for statistical analysis of risk factors, with 3 months and 60 months as the cut-off time points and all-cause death as the primary endpoint.Results: Among the 1252 included patients, 138 patients had died by the end of follow-up (11.0%). Age at diagnosis, C-reactive protein (CRP) levels and total bilirubin (TBIL) were time-dependent risk factors for mortality. Within 3 months of follow-up, age > 65 years had no effect on mortality, but after 3 months of follow-up, the mortality risk in patients aged > 65 years increased over time (HR 3.97, 95% CI 2.57– 6.13; HR 16.63, 95% CI 5.53– 50.03). CRP > 6.5 mg/L increased the risk of mortality within 3 months (HR=11.45, 95% CI 2.52– 51.95), followed by 3– 60 months (HR=2.94, 95% CI 1.94– 4.45), but did not affect survival after 60 months of follow-up. TBIL > 18.01 μmol/L increased the risk of mortality in pSS patients within 3– 6 months (HR=2.30, 95% CI 1.42– 3.79) but did not increase the risk of mortality in patients with pSS within 3 months of follow-up or after 60 months.Conclusion: pSS patients with a CRP level > 6.5 mg/L have an 11-fold increased risk of near-term death, whereas pSS patients older than 65 years of age at diagnosis have a 16-fold increased risk of long-term death.Keywords: sjögren’s syndrome, mortality, risk factors, inflammation