TOPLINE:

In patients with systemic lupus erythematosus (SLE), a higher dose of hydroxychloroquine (HCQ) was linked to lower risks for coronary artery disease and venous thromboembolism than a lower dose of HCQ, and no differences were observed in the risks for stroke, kidney failure, cancer, or overall HCQ retinopathy; however, a higher risk for retinopathy was seen in older adults.

METHODOLOGY:

• This nationwide target trial emulation study used Taiwan’s health insurance data (2010-2021) to compare the effectiveness and safety of high and low doses of HCQ in patients with SLE.
• Researchers included new HCQ users with SLE aged 10 years or older who had no other systemic autoimmune diseases or prior study outcomes. On the basis of the first HCQ prescription, ≥ 400 mg/d was defined as a higher dose of HCQ and < 400 mg/d was defined as a lower dose of HCQ.
• Among the patients included, 878 received higher-dose HCQ and 22,405 received lower-dose HCQ. After propensity weighting, the cohorts included 21,963 patients in the higher-dose group and 23,293 in the lower-dose group (mean ages, 43.1 and 43.5 years; 85% and 85.4% women, respectively).
• Outcomes were coronary artery disease, ischemic stroke, venous thromboembolism, end-stage renal disease, malignancy, and HCQ retinopathy.
• Patients were followed up from the start of HCQ until the earliest of an outcome, loss to follow-up, death, or December 2021, with a median follow-up duration of 5.35 years for the higher-dose group and 6.15 years for the lower-dose group.

TAKEAWAY:

• Compared with lower-dose HCQ, higher-dose HCQ was associated with a 14% lower risk for coronary artery disease (hazard ratio [HR], 0.86; 95% CI, 0.80-0.93) and a 60% lower risk for venous thromboembolism (HR, 0.40; 95% CI, 0.33-0.49).
• No significant differences were found between higher and lower doses of HCQ in terms of risks for ischemic stroke, end-stage renal disease, malignancy, and HCQ retinopathy.
• Among patients aged 45 years or older, higher-dose HCQ was associated with an increased risk for HCQ retinopathy (HR, 1.87; 95% CI, 1.45-2.42).
• Findings were robust across multiple sensitivity analyses and remained consistent when using alternative dose thresholds.

IN PRACTICE:

“Our study emphasizes the need for weighing the benefits and risks of optimal HCQ dosage in managing SLE,” the authors wrote.

SOURCE:

This study was led by Brian Meng-Hsun Li, National Cheng Kung University, Tainan, Taiwan. It was published online on December 21, 2025, in Arthritis & Rheumatology.

LIMITATIONS: 

Residual confounding could not be ruled out because of missing information on smoking status, obesity, contraceptive use, laboratory values, and detailed SLE activity. Screening rates for HCQ retinopathy were relatively low, which may have underestimated retinopathy risk. The small sample size of patients using higher-dose HCQ limited evaluation of rare outcomes.

DISCLOSURES:

This study was supported in part by grants from the National Science and Technology Council of Taiwan. The authors reported having no financial relationships with any organizations that might have influenced the work in the previous 3 years.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.