Associations between Hydroxychloroquine(HCQ) dose and the risk of flares in systemic lupus erythematosus

Objectives: To evaluate the relationship between Hydroxychloroquine (HCQ) dosage and the incidence of flares in Systemic Lupus Erythematosus (SLE). Methods: In this retrospective cohort study, 703 SLE patients from multiple sites in China were analyzed from October 2020 to May 2023. Patients with a SLEDAI-2K score ≥4 were categorized into low-dose (≤6.7 mg/kg/day) and high-dose (>6.7 mg/kg/day) HCQ groups. The primary outcome was an SLE flare incidence, determined by therapy augmentation, an SLEDAI-2000 increase of ≥4 points, or hospitalization. Results: Among the 703 patients, 45.5% experienced flares. P atients in the high-dose group had a significantly lower flare incidence (41.1%) compared to the low-dose group (51%, P =0.009). Cox regression analyses showed that higher HCQ doses were consistently associated with a reduced risk of flares (HR 0.93, 95% CI 0.86–0.99, P =0.03). When stratified by HCQ dosage, patients receiving≥6.7mg/kg/day had a lower risk of flares compared to those receiving <6.7mg/kg/day, with a hazard ratio of 0.76 (95% CI 0.61–0.96, P =0.019). Kaplan-Meier survival analysis confirmed a longer flare-free survival in the high-dose group ( P =0.022). The smoothed dose HR curve indicated a clear trend of reduced flare risk for increased hydroxychloroquine dosages. Subgroup analyses show a clear trend without significant interaction effects. Conclusions: Higher HCQ dosages are associated with a reduced risk of SLE flares and improved flare-free survival, supporting the optimization of HCQ dosing in SLE management. Keywords: hydroxychloroquine, flare, lupus, systemic