Low hydroxychloroquine blood levels linked to thrombotic events in lupus
Click Here to Manage Email Alerts
A mean hydroxychloroquine blood level of more than 1,068 ng/mL is associated with a 69% reduction in thrombotic events, compared with blood levels of less than 648 ng/mL, among patients with systemic lupus erythematosus, according to data.
“Despite its widespread use since the 1950s, optimal dosing of HCQ in SLE is unknown,” Michelle Petri, MD, MPH, of Johns Hopkins University School of Medicine, and colleagues wrote in Arthritis & Rheumatology. “More recently, concern about retinopathy increased after a retrospective Kaiser-Permanente study. The retrospective Kaiser-Permanente study was the basis for the revised American Academy of Ophthalmology (AAO) guidance to limit hydroxychloroquine dosing to less than 5 mg/kg absolute body weight.”
“The Kaiser-Permanente study, however, was based on pharmacy dispensing records and not on the prescribed dose (which is higher due to partial adherence),” they added. “A study of 412 SLE patients recently suggested that empirical dose reduction following AAO guidelines was not associated with increased short-term risk of lupus related end-organ damage, but importantly did not look at therapeutic drugs levels or thromboembolic events.”
To analyze the utility of hydroxychloroquine blood monitoring in predicting thrombosis risk among patients with SLE, Petri and colleagues examined data from the Hopkins Lupus Cohort, a longitudinal study of SLE outcomes. In all, the researchers included 739 cohort participants with SLE and one or more hydroxychloroquine blood measurement. These measurements were serially quantified from EDTA whole blood via liquid chromatography‐tandem mass spectrometry.
The researchers used t-tests to compare mean hydroxychloroquine blood levels recorded prior to thrombosis, or until the last visit, between participants with and without thrombosis. They then used pooled logistic regression to examine the link between thrombosis rates and hydroxychloroquine blood level.
According to the researchers, thrombosis occurred in 5.1% of included participants. Mean hydroxychloroquine blood levels were lower among participants who developed thrombosis, at 720 ± 489 ng/mL, compared with those without thrombosis, at 935 ± 580 ng/mL (P = .025). In addition, rates of thrombosis were reduced by 12% for every 200 ng/mL increase in the most recent hydroxychloroquine blood level (0.87; 95% CI, 0.78- 0.98), and by 13% for mean hydroxychloroquine blood level (rate ratio = 0.87; 95% CI, 0.76-1).
Participants with mean hydroxychloroquine blood levels of more than 1,068 ng/mL demonstrated a 69% reduction in thrombotic events, compared with those with a mean of less than 648 ng/mL (0.31; 95% CI, 0.11-0.86). This finding remained significant after adjusting for confounders (0.34; 95% CI, 0.12-0.94).
“We need to move away from the weight-based dosing recommendations from ophthalmology to personalized medicine — meaning let’s adopt routine use of HCQ blood levels,” Petri told Healio Rheumatology. “Low levels usually mean nonadherence. Using the Hopkins assay, the level needs to be around 1,000 to prevent thrombosis. The upper tertile on the Hopkins assay indicated increased risk of retinopathy. We shouldn’t be flying blind with HCQ dosing.”
Perspective
Back to Top
David A. McLain, MD, MACR, FACP, FRCP
Hydroxychloroquine (HCQ) is a remarkable drug. The first report in rheumatology on the use of antimalarials appeared in 1951 when Francis Page, MD, reported that lupus symptoms were improved with quinacrine. Two years later, James Charles Shee, MD, reported that solders with rheumatoid arthritis or lupus who were receiving prophylaxis for malaria with chloroquine showed clinical improvement. In 1955, more than 65 years ago now, hydroxychloroquine, with fewer side effects that chloroquine, was approved by the FDA for RA and lupus.
In 1991, the first prospective randomized study of hydroxychloroquine, which confirmed efficacy in lupus, was completed and published by John Esdaile, MD, MPH, and colleagues. In lupus, data shows that hydroxychloroquine may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage and prevent the thrombotic effects of antiphospholipid antibodies.
In 2008, a nested, case-controlled study aiming to identify factors predictive of infectious complications reported that SLE patients treated with antimalarial agents had a lower risk of major infections. Antimalarials protect against thrombotic events, improve lipid profiles and glucose, and prevent renal damage, apparently resulting in reduced cardiovascular risk, for which SLE is an independent risk factor.
Ultimately, an increased rate of survival has been reported in SLE patients taking antimalarial agents. A population-based, case-controlled study from 2019 demonstrated that mortality risk increased almost fourfold in people who had to stop taking their hydroxychloroquine; the drug also appears to be safe and effective in pregnant patients, reducing flares during this time and decreasing the risk of cardiac neonatal lupus.
This paper by Dr. Petri again documents the anti-thrombotic effect of hydroxychloroquine. It also shows that prescribed hydroxychloroquine doses do not predict hydroxychloroquine blood levels. This is an area of interest that I am sure will be researched further.
Collapse
Read more about
Click Here to Manage Email Alerts