Weighing Dose-Related Benefits and Risks of Hydroxychloroquine Treatment in Patients With Systemic Lupus Erythematosus

Objective: To weigh higher-dose hydroxychloroquine (HCQ; ≥400 mg/day) and lower-dose HCQ (<400 mg/day) for effectiveness and safety among patients with systemic lupus erythematosus (SLE). Methods: This nationwide study retrieved data from Taiwan's National Health Insurance Research Database from 2010 to 2021. We included patients with SLE aged over 10 years and initiating HCQ who had no other systemic autoimmune disease at baseline and no historical outcomes of interest. Patients were classified into higher-dose (≥400 mg/day) or lower-dose (<400 mg/day) treatment strategies based on the dosage of their first HCQ prescription. The outcomes were coronary artery disease (CAD), ischemic stroke, venous thromboembolism (VTE), end-stage renal disease, malignancy, and HCQ retinopathy. Results: Eight hundred seventy-eight (3.77%) patients taking higher-dose HCQ and 22,405 (96.22%) taking lower-dose HCQ were included. After inverse probability weighting, higher-dose HCQ was associated with lower risks of CAD (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.80–0.93) and VTE (HR 0.40, 95% CI 0.33–0.49). We found no dose-related difference in the risk of ischemic stroke, end-stage renal disease, malignancy, and HCQ retinopathy through a mean follow-up of six years, except for the HCQ retinopathy among patients with SLE aged over 45 years (HR 1.87, 95% CI 1.45–2.42). Conclusion: For patients with SLE, higher-dose HCQ improves effectiveness, with reduced risks of CAD and VTE. There was no dose-related difference in the risk of HCQ retinopathy for patients with SLE aged younger than 45 years. Our study emphasizes the need for weighing the benefits and risks of optimal HCQ dosage in managing SLE. (Figure presented.).