Background: Hydroxychloroquine (HCQ) has a primary role in the treatment of systemic lupus erythematous (SLE). Beyond its pleiotropic immunomodulatory effects on Toll-like receptor and type I interferon signaling, HCQ use has been found to be protective for thrombosis in SLE (1). Optimal dosing of HCQ in SLE is unknown. The longitudinal measurement of HCQ blood levels may provide an opportunity to individualize weight-based dosing strategies and reduce risk of toxicity.
Objectives: Examine the association of HCQ blood levels with thrombotic events in a longitudinal SLE cohort.
Methods: 812 SLE patients with HCQ blood level measured prior to the thrombosis were included: 93% female, 43% African-American, 46% Caucasian. HCQ blood levels were quantified by liquid chromatography-tandem mass spectrometry. Mean HCQ blood levels (± standard deviation) over all cohort visits prior to occurrence of thrombosis were calculated for each patient. Thromboses were defined as venous (DVT/PE or other venous) or arterial thrombosis (stroke, myocardial infarction, digital gangrene or other arterial).
Results: Thrombosis had occurred during prospective follow up in 43 patients (5.5%), venous in 3.0% and arterial in 2.9%. Lupus anticoagulant was strongly associated with a history of any thrombosis (OR 3.25, p<0.0001), venous thrombosis (OR 3.53, p<0.0001), and arterial thrombosis (OR 3.08, p<0.0001). A prospective analysis shows that for any thrombosis and for venous thrombosis, the HCQ blood level was significantly lower (Table 1). Higher prescribed doses of HCQ (as opposed to HCQ blood levels) were also associated with decreased odds of any thrombosis and venous thrombosis in a separate cross-sectional analysis (OR 0.88, p=0.04 and OR 0.83, p=0.009, respectively for each 1 mg/kg increase in prescribed HCQ).
Conclusion: HCQ blood levels are inversely associated with risk of any thrombosis and of venous thrombosis in patients with SLE in a prospective analysis. Reduction of HCQ dosing, as suggested by the American Academy of Ophthalmologists (2), could reduce or eliminate the benefit of hydroxychloroquine to prevent thrombosis.
References: Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody–positive patients. Curr Rheumatol Rep 2011;13:77–80.
Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016;123:1386–1394.
Acknowledgments: The Hopkins Lupus Cohort is supported by NIH Grant RO1 AR069572
Disclosure of Interests: Michelle A Petri Grant/research support from: GSK, Eli Lilly and Company, Consultant of: Eli Lilly and Company, Maximilian Konig: None declared, Jessica Li: None declared, Daniel Goldman: None declared
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