Predictors of short-term treatment response to belimumab in childhood-onset systemic lupus erythematosus: a real-world retrospective, single-center clinical study in China

The belimumab treatment response in patients with childhood-onset systemic lupus erythematosus (cSLE) is highly variable. Pediatric-specific predictors remain poorly defined. This study aimed to identify predictors associated with belimumab response to optimize patient selection in a real-world cSLE cohort. We retrospectively analyzed 100 cSLE patients treated with belimumab combined with standard care between January 2021 and August 2025 at our center. Response was defined as attainment of SLE Responder Index-4 (SRI-4) at the 8th belimumab infusion. Baseline demographic, clinical and laboratory characteristics were compared between responders ( n = 83) and non-responders ( n = 17). Independent predictors were identified using Firth’s bias-reduced penalized logistic regression. Generalized estimating equations (GEE) with adjustment for concurrent glucocorticoid doses was used to evaluate longitudinal changes in lymphocyte subsets and inflammatory cytokines. The SRI-4 response rate was 83% in our cohort. Univariate analysis indicated that responders had significantly higher baseline 24-hour urine protein, anti-dsDNA antibody titers, ferritin, LDH and AST, along with lower complement C3/C4, hemoglobin, platelet and absolute eosinophil counts. Additionally, the proportion of female patients, and the prevalence of oral ulcers, arthritis and positive anti-nucleosome antibodies were higher in responders. Multivariate Firth-corrected logistic regression identified 24-hour urine protein quantification as the sole predictor of a favorable response (OR = 2.271, 95%CI 1.093–4.721, P = 0.028). In GEE analysis, CD4 + and CD8 + T-cell counts increased significantly over time in both groups irrespective of response ( P < 0.001), while CD19 + B-cell count was significantly modulated by concurrent glucocorticoid dosage ( P = 0.025). There was no significant group-by-time interaction for lymphocyte subsets and inflammatory cytokines after false discovery rate correction. Baseline 24-hour urine protein quantification is an exploratory predictor of short-term SRI-4 response to belimumab in cSLE. Further validation in multi-center cohorts is needed to enable a more personalized application of belimumab.