High-Dose HCQ Tied to Better Symptom Control in SLE With Lower Adverse CV Events: Study
Taiwan: Analysis of national data from Taiwan shows that hydroxychloroquine (HCQ), despite known long-term risks such as retinopathy, remains a cornerstone of lupus treatment. In patients with systemic lupus erythematosus (SLE), HCQ doses of ≥400 mg/day were associated with better symptom control and a lower risk of cardiovascular disease. Importantly, in patients younger than 45 years, higher doses did not increase the risk of retinopathy compared with lower doses, suggesting a favorable benefit–risk profile in this population.
Hydroxychloroquine has long been a foundational therapy in SLE because of its immunomodulatory effects and its role in reducing disease flares, organ damage, and mortality. However, uncertainty persists regarding the optimal dose that maximizes clinical benefits while minimizing long-term toxicity, particularly retinal damage.
Addressing this concern, researchers led by Brian Meng-Hsun Li, MClinPharm, from the Population Health Data Center, School of Pharmacy, National Cheng Kung University, Taiwan, conducted a large nationwide analysis to evaluate dose-related effectiveness and safety of HCQ in real-world clinical practice.
In the study, published in Arthritis & Rheumatology, the investigators analyzed data from Taiwan’s National Health Insurance Research Database spanning 2010 to 2021. The study included patients older than 10 years who had a diagnosis of SLE and were newly initiated on HCQ, with no other systemic autoimmune diseases or prior history of key clinical outcomes at baseline.
Based on the dosage of their first HCQ prescription, patients were categorized into a higher-dose group (≥400 mg/day) or a lower-dose group (<400 mg/day). The researchers then followed patients for major outcomes, including coronary artery disease (CAD), ischemic stroke, venous thromboembolism (VTE), end-stage renal disease (ESRD), malignancy, and HCQ-associated retinopathy.
The key findings were as follows:
- Only a small fraction of the more than 23,000 patients received higher-dose hydroxychloroquine, indicating cautious prescribing in routine practice.
- After adjustment for baseline differences, higher-dose hydroxychloroquine was linked to a significantly lower risk of cardiovascular events.
- Patients taking ≥400 mg/day had reduced risks of coronary artery disease and venous thromboembolism compared with those on lower doses.
- No dose-related differences were observed in the risks of ischemic stroke, end-stage renal disease, or malignancy over a mean follow-up of six years.
- Overall rates of hydroxychloroquine-associated retinopathy were similar between higher- and lower-dose groups.
- Age influenced retinopathy risk, with higher doses associated with increased risk in patients older than 45 years.
- No increased retinopathy risk with higher-dose hydroxychloroquine was seen in patients younger than 45 years.
The authors conclude that higher-dose HCQ offers meaningful clinical advantages for patients with SLE, particularly through reductions in CAD and VTE risk, without added retinal risk in those under 45 years of age. These findings highlight the importance of individualized dosing strategies, balancing therapeutic benefits against potential harms, and underscore the need for age-specific risk assessment and regular ophthalmologic monitoring when prescribing HCQ.
Reference:
Meng-Hsun Li, B., Hung, H., Yang, C., Lin, J., Chia-Cheng Lai, E., & Weng, Y. Weighing dose-related benefits and risks of hydroxychloroquine treatment in systemic lupus erythematosus patients. Arthritis & Rheumatology. https://doi.org/10.1002/art.70022
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