To explore the efficacy and safety of belimumab in serologically active clinically quiescent (SACQ) systemic lupus erythematosus (SLE) patients. To explore the baseline predictors of belimumab treatment outcomes.

SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were prospectively and consecutively enrolled from July 2021 to August 2024. Simultaneously, SACQ SLE patients receiving only SoC, after propensity score matching (PSM), were enrolled as controls. Clinical data were collected, and disease assessments were conducted regularly. Patients with at least 12-month follow-up time were included in the analyses. The difference between groups, baseline predictors for treatment response were evaluated.

A total of 148 SLE were enrolled, with 25 in the SACQ state at baseline. Among them, 92 achieved the SRI-4 response, with a median time of 3 months. Compared with non-responders, responders had shorter disease duration, higher SLEDAI-2K scores, a larger proportion of newly diagnosed patients, and lower SACQ state frequency. They also exhibited higher prevalence of renal involvement, musculoskeletal manifestations, cutaneous lesions, and constitutional symptoms, along with higher B-cell ratios, absolute counts, and daily prednisone dosage. GEE analysis of SACQ patients over 12 months showed that though trends of complement C3, C4, anti-dsDNA antibody titer was similar in two groups. The interaction between group and time was statistically significant for complement C3 (β=7.95, 95% CI: 2.33–13.56, P=0.006 at 6 months; β=6.05, 95% CI: 0.29–11.82, P=0.040 at 12 months), complement C4 (β=2.06, 95% CI: 0.13–3.98, P=0.036 at 6 months; β=2.83, 95% CI: 0.58–5.09, P=0.014 at 12 months), and anti-dsDNA antibody titer (β=–32.95, 95% CI: –59.84 to –6.05, P=0.016 at 6 months; β=–35.53, 95% CI: –69.69 to –1.36, P=0.042 at 12 months). Besides, a trend toward prednisone dosage reduction was observed at 6 months, but this was not significant at 12 months. No severe adverse events were observed during follow up for SACQ patients. 

Addition of belimumab could improve serological parameters and favor the glucocorticoids tapering for SACQ patients, though more definitive evidence were needed. Further, belimumab may be a beneficial add-on therapy for newly diagnosed SLE patients with higher disease activity, presence of renal, musculoskeletal, cutaneous or constitutional manifestations, and elevated baseline B lymphocyte ratios.