Maintaining an average hydroxychloroquine whole blood level above 1,068 ng/mL significantly reduced the risk of thrombosis in adults with systemic lupus erythematosus, based on data from 739 patients.
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Hydroxychloroquine (HCQ) is a common treatment for systemic lupus erythematosus (SLE); studies suggest that it may protect against thrombosis, but the optimal dosing for this purpose remains unknown, wrote Michelle Petri, MD, of Johns Hopkins University, Baltimore, and colleagues. In a study published in Arthritis & Rheumatology, the researchers examined data on HCQ levels from 739 adults with SLE who were part of the Hopkins Lupus Cohort, a longitudinal study of outcomes in SLE patients. Of these, 38 (5.1%) developed thrombosis during 2,330 person-years of follow-up.
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Dr. Michelle Petri
Overall, the average HCQ blood level was significantly lower in patients who experienced thrombosis, compared to those who did not (720 ng/mL vs. 935 ng/mL; P = .025). “Prescribed hydroxychloroquine doses did not predict hydroxychloroquine blood levels,” the researchers noted.
In addition, Dr. Petri and associates found a dose-response relationship in which the thrombosis rate declined approximately 13% for every 200-ng/mL increase in the mean HCQ blood level measurement and for the most recent HCQ blood level measurement after controlling for factors that included age, ethnicity, lupus anticoagulant, low C3, and hypertension.
In a multivariate analysis, thrombotic events decreased by 69% in patients with mean HCQ blood levels greater than 1,068 ng/mL, compared to those with average HCQ blood levels less than 648 ng/mL.
The average age of the patients at the time HCQ measurements began was 43 years, 93% were female, and 46% were White. Patients visited a clinic every 3 months, and HCQ levels were determined by liquid chromatography-tandem mass spectrometry.
“Between-person and within-person correlation coefficients were used to measure the strength of the linear association between HCQ blood levels and commonly prescribed HCQ doses from 4.5 to 6.5 mg/kg,” the researchers said.
Higher doses of HCQ have been associated with increased risk for retinopathy, and current guidelines recommend using less than 5 mg/kg of ideal body weight, the researchers said. “Importantly, 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,” they emphasized.
The study findings were limited by several factors, including the observational design and potential confounding from variables not included in the model, as well as the small sample size, single site, and single rheumatologist involved in the study, the researchers noted.
The results suggest that aiming for a blood HCQ level of 1,068 ng/mL can be done safely to help prevent thrombosis in patients with SLE, the researchers said. “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,” they concluded.
The study was supported in part by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no relevant financial conflicts to disclose.
SOURCE: Petri M et al. Arthritis Rheumatol. 2021 Jan 6. doi: 10.1002/ART.41621.