Abstract
Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with significant morbidity and premature mortality. As patients with SLE often suffer from multiple comorbid conditions, evaluating the overall health burden is critical for improving risk stratification and long-term outcomes. The Charlson Comorbidity Index (CCI) is a widely used tool for quantifying the burden of comorbidity. This systematic review and meta-analysis aimed to assess the prognostic value of the CCI for all-cause mortality in adult patients with SLE. Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA 2020 guidelines. Three databases (PubMed, Embase, and Web of Science) were searched up to May 2025. Three studies (n = 1175 participants) met the inclusion criteria. Eligible studies included adult SLE populations that evaluated the comorbidity burden using the CCI and reported all-cause mortality. Study characteristics and effect sizes were extracted, and a fixed-effects model (after considering both random- and fixed-effects approaches) was applied to calculate pooled odds ratios (ORs). Risk of bias was assessed using the Newcastle-Ottawa Scale. Results: Three observational studies (n = 1175 participants) met the inclusion criteria. All demonstrated a significant association between higher CCI scores and increased all-cause mortality. The pooled OR for mortality in patients with a high comorbidity burden was 3.92 (95% CI: 2.74-5.60), with no observed heterogeneity (I(2) = 0%). The risk of bias was moderate to high across all studies. Conclusions: Multimorbidity, as measured by the CCI, is a strong independent predictor of mortality in SLE. Integrating comorbidity assessment into rheumatology care may enhance prognostic evaluation, guide personalized treatment, and support interdisciplinary management strategies for patients with complex disease profiles.