NEW RESEARCH has revealed that low hydroxychloroquine blood levels and poor long-term adherence significantly raise atherosclerotic cardiovascular disease risk in patients with systemic lupus erythematosus (SLE).
Hydroxychloroquine has remained the cornerstone of systemic lupus erythematosus management, with benefits that have extended beyond disease control to include protection against atherosclerotic cardiovascular disease.
Although hydroxychloroquine blood levels reflect recent drug exposure and long-term intake reflects medication adherence, how longitudinal changes in both measures relate to SLE atherosclerotic cardiovascular disease risk over time has remained unclear until now.
Researchers conducted a prospective longitudinal study of 248 adults with systemic lupus erythematosus from the Wisconsin cohort, all meeting 2019 American College of Rheumatology/EULAR classification criteria and taking hydroxychloroquine. Participants completed baseline and one-year follow-up visits.
Long-term hydroxychloroquine intake was estimated using proportion of days covered, while whole-blood hydroxychloroquine levels served as a marker of recent exposure. Ten-year atherosclerotic cardiovascular disease risk was calculated at both time points using the PREVENT calculator, with multivariable linear regression used to assess associations between exposure patterns and risk.
Patients with very low hydroxychloroquine blood levels (below 200 ng/mL) combined with low long-term intake (proportion of days covered below 80%) had significantly higher cardiovascular risk at baseline, with a mean predicted ten-year risk of 6.6%, an increase of 2.1 percentage points. Patients who remained in or transitioned into these low-exposure categories over one year had the highest predicted risk at follow-up, at 5.7%.
These findings have highlighted that sustained hydroxychloroquine adherence and therapeutic blood levels may help lower SLE atherosclerotic cardiovascular disease risk while avoiding unnecessary addition of preventive therapies such as statins. Monitoring both proportion of days covered and blood levels together has been shown to capture complementary information, as adherence reflects intake over time while blood levels reflect individual absorption, metabolism, and clearance. Clinicians may consider dual monitoring to guide targeted interventions and reduce polypharmacy risk in this population.
Reference
Garg S et al. Optimizing hydroxychloroquine blood levels and long-term hydroxychloroquine intake could lower atherosclerotic cardiovascular disease risk and prevent polypharmacy in systemic lupus erythematosus. Arthritis Care Res. 2026;DOI:10.1002/acr.80128.
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