medwireNews: Among patients with systemic lupus erythematosus (SLE) receiving treatment with hydroxychloroquine, low drug levels in the blood are associated with an elevated risk for arterial and venous thrombosis events, researchers report.
“Thrombosis in [SLE] remains a major cause of morbidity and mortality,” and previous studies suggest that hydroxychloroquine reduces thrombosis risk, say Michelle Petri and colleagues from the Johns Hopkins University School of Medicine in Baltimore, Maryland, USA.
They note, however, that “optimal dosing of [hydroxychloroquine] in SLE is unknown,” and that the American Academy of Ophthalmology issued revised guidance limiting dosing to less than 5 mg/kg due to concerns about retinopathy risk with higher doses.
The current study included 739 SLE patients (93% women) with an average age of 43 years at baseline. During 2330 person–years of follow-up, 5.1% of these patients experienced incident thrombosis, giving an overall event rate of 16.3 per 1000 person–years.
As reported in Arthritis & Rheumatology, people who developed thrombosis had significantly lower average hydroxychloroquine blood levels than those who did not, at 720 ng/mL and 935 ng/mL, respectively. Each 200 ng/mL increase in hydroxychloroquine levels was associated with a 13% reduction in thrombosis risk after adjustment for a range of confounders including age, ethnicity, and arterial hypertension.
Moreover, when average blood hydroxychloroquine levels were divided into tertiles, people with levels above 1068 ng/mL had a significant 66% lower risk for thrombosis than those with levels below 648 ng/mL, at rates of 6.5 versus 20.6 events per 1000 person–years. Patients with intermediate (648–1068 ng/mL) blood hydroxychloroquine levels had a comparable thrombosis risk to those in the lowest tertile (19.3 vs 20.6 events per 1000 person–years).
“Together, these data suggest that hydroxychloroquine whole blood levels were predictive of thrombotic events in SLE in a dose-dependent manner,” say Petri and team, adding that “similar trends were observed for both arterial and venous thrombosis.”
The team points out that “there was no correlation between the prescribed dose and the hydroxychloroquine blood level over the range (4.5 to 6.5 mg/kg) used in clinical practice, highlighting the need for personalized hydroxychloroquine drug level-guided therapy and dose adjustment.”
Noting that hydroxychloroquine blood levels of 1068 ng/mL were associated with a significantly reduced thrombosis risk, Petri et al believe it “should be possible to target this level” while avoiding higher doses previously associated with retinopathy risk.
They conclude: “Routine clinical integration of hydroxychloroquine blood level measurement offers an opportunity for personalized drug dosing and risk management beyond rigid empirical dosing recommendations in patients with SLE.”
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