Hanan Hassan Fouad

Objectives
The study aimed to examine the frequency, causes, and predictors of mortality in a cohort of Egyptian systemic lupus erythematosus (SLE) patients and compare mortality causes and the survival rate in our cohort to African, Arabic, and Mediterranean studies.

Patients and methods
In this retrospective study, a review of medical records of 563 SLE patients (516 females, 47 males; median of age: 32 [IQR: 26-38 years]; range, 14 to 63 years) fulfilling the 1997 American College of Rheumatology (ACR) criteria between January 2015 and December 2019 was done. The data extracted included demographic, clinical, and laboratory features, treatments used, disease activity as measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage index as measured by Systemic Lupus International Collaborating Clinics (SLICC) damage index. Causes of mortality were also reported.

Results
Out of 563 reviewed medical records, 50 (8.9%) patients died. Infection (28%) and organ damage (18%) were the most commonly reported causes of death. Multivariate Cox regression analysis showed that patients with cardiac manifestations, renal failure, those receiving higher doses of either oral (in their last visit) or intravenous (higher cumulative pulse steroids) steroids were at increased risk of mortality (p=0.011, p<0.001, p=0.01, and p<0.001, respectively; 95% confidence intervals 7.2, 63.9, 1.2, and 1.09, respectively). The overall survival at 5, 10, 15, and 20 years was 96.6%, 93.3%, 91.0%, and 83.2%, respectively, and 56.2% at 25 years until the end of the follow-up.

Conclusion
Cardiac manifestations, renal failure, and higher steroid doses were independent predictors of mortality in our cohort. As in most African countries, infection was the main cause of death in our study; however, the mortality rate and the five-year survival among our cohort were better than in African (sub-Saharan) countries and similar to Arabic and Mediterranean countries.

BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.

METHODS: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.

FINDINGS: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death.

INTERPRETATION: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.

FUNDING: Novartis.