REFILE-Monitoring hydroxychloroquine blood levels may help predict thrombosis risk in SLE

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(Corrects typo in para 5 of story originally posted Jan 8.)

By Megan Brooks

NEW YORK (Reuters Health) - Monitoring blood levels of hydroxychloroquine can help predict the risk of thrombosis in patients with systemic lupus erythematosus (SLE), a new study suggests.

Among SLE patients receiving HCQ, low blood drug levels were associated with an increased risk for arterial and venous thrombosis events, researchers report in Arthritis and Rheumatism.

"Hydroxychloroquine blood levels can be used to monitor adherence, benefits, and risks in lupus," lead author Dr. Michelle Petri of Johns Hopkins University School of Medicine, in Baltimore, Maryland, said in a statement.

In a longitudinal study, she and her colleagues serially quantified HCQ levels from whole blood in 739 patients with SLE. During 2,330 person-years of follow-up, 38 (5.1%) developed a blood clot, for an overall thrombosis event rate of 16.3 per 1,000 person-years.

Average HCQ blood levels were lower in patients with than without thrombosis (720 vs. 935 ng/mL, P=0.025). Thrombosis rates were reduced by 13% for every 200 ng/mL increase in the mean HCQ blood level and by 12% for every 200 ng/mL increase in the most recent HCQ blood level.

Thrombosis events were reduced by 69% in patients with average HCQ blood levels higher than 1,068 ng/mL versus lower than 648 ng/mL (P=0.024) and this finding remained significant after confounder adjustment.

Together, the findings suggest that HCQ whole-blood levels are predictive of thrombotic events in SLE patients in a dose-dependent manner, the researchers write.

Of note, they add, there was no correlation between the prescribed HCQ dose and HCQ blood level over the range used in clinical practice (4.5 to 6.5 mg/kg), "highlighting the need for personalized hydroxychloroquine drug level-guided therapy and dose adjustment."

Noting that HCQ blood levels of 1068 ng/mL were associated with significantly reduced thrombosis risk, the researchers say "it should be possible to target this level and still avoid higher doses previously associated with retinopathy risk."

"I think there should now be a paradigm change in how we use hydroxychloroquine for SLE," Dr. Petri told Reuters Health by email.

"We need to move away from (dosing) rules based on weight alone and use blood levels to guide dosing because low levels indicate nonadherence. Levels around 1000 (in our assay) are needed to insure benefit and the highest tertile should be avoided to reduce risk of retinopathy," Dr. Petri said.

SOURCE: https://bit.ly/2Xgdsnt Arthritis and Rheumatism, online January 5, 2021.

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