Abstract
OBJECTIVES: To evaluate the relationship between Hydroxychloroquine (HCQ) dosage and the incidence of flares in Systemic Lupus Erythematosus (SLE) flare incidence. METHODS: This retrospective cohort study analysed 703 SLE patients (Systemic Lupus Erythematosus Disease Activity Index 2000, SLEDAI-2 K ≥ 4) from multiple Chinese centres (2020-2023). Patients were stratified by HCQ dose into low-dose (≤ 6.5 mg/kg/day) and high-dose (> 6.5 mg/kg/day) HCQ groups. The primary outcome was SLE flare incidence (therapy augmentation, SLEDAI-2 K increase ≥ 4, or SLE-related hospitalisation. RESULTS: Among the 703 patients, 45.5% experienced flares. Flare incidence was significantly lower in the high-dose group (41.0% vs. 51.5%, P = 0.006). High-dose HCQ reduced flare risk (fully adjusted HR 0.77, 95% CI 0.61-0.97, P = 0.024) and prolonged flare-free survival (P = 0.011). Dose-response analysis showed a linear reduction in flare risk with increasing HCQ doses. Sensitivity analyses using 5 mg/kg/day cutoff and cumulative dose yielded consistent results. CONCLUSIONS: Higher HCQ dosages are associated with a reduced SLE flares risk, and improved flare-free survival, supporting individualized dosing within safety guidelines. CLINICAL TRIAL REGISTRATION: Not applicable.