A blood-level reference range of 750-1,200 ng/mL of hydroxychloroquine (HCQ) has been linked with 71% lower odds of active lupus, new research suggests.
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Researchers, led by Shivani Garg, MD, assistant professor of rheumatology at the University of Wisconsin–Madison, also found that maintaining levels within that range lowered the odds for flares by 26% over 9 months of follow-up.
The findings, published in Arthritis Care & Research, could help clinicians personalize HCQ doses to maximize efficacy for each patient.
UW Health
Dr. Shivani Garg
HCQ levels in whole blood and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were measured during a baseline visit and again during a routine follow-up visit.
Among 158 baseline patient visits, 19% of the patients had active lupus. Researchers longitudinally followed 42 patients using convenience sampling, and among those patients, 7 (17%) had flares at the follow-up visit.
Michelle Petri, MD, MPH, director of the Johns Hopkins Lupus Center in Baltimore, called the findings that suggest upper and lower efficacy and safety boundaries “very important.”
The findings highlight that guidelines for dosing don’t match efficacy needs, said Dr. Petri, who was not involved with the study.
“HCQ dosing has been under threat by guidelines insisting that the dose should be < 5 mg/kg even though this does not correlate with efficacy,” she said. “Basically, if we dose too low, the patient loses efficacy. If we dose too high, the risk of retinopathy increases, so this paper hones down the sweet spot.”
A 2014 study identified a higher eye toxicity risk with HCQ doses > 5 mg/kg per day, and the American Academy of Ophthalmology followed with guidelines for HCQ retinopathy screening that recommended reducing HCQ to ≤ 5 mg/kg per day.
Dr. Petri said that the range Dr. Garg and colleagues identified corroborates findings in one of her team’s studies.
That paper showed that thrombotic events dropped by 69% in patients with average HCQ blood levels ≥ 1,068 ng/mL vs. those with levels < 648 ng/mL (relative risk, 0.31; 95% confidence interval, 0.11-0.86; P = .024).
Dr. Garg and colleagues write that current lupus treatment guidelines do not universally recommend blood level monitoring for HCQ “as different cut-points have been used to define therapeutic HCQ blood levels and an effective range of HCQ levels with upper and lower bounds for efficacy has not been extensively examined.”
When to start checking levels
Blood levels of HCQ can be checked for any patient, although 1-3 months after starting the medication may be best to get steady levels, Dr. Garg told this news organization.
Dr. Petri said that she recommends HCQ whole blood levels be checked routinely for maximum dosing efficacy “but also to identify patients who are missing so many doses that they are subtherapeutic.”
She noted that nonadherence is a major issue among patients with systemic lupus erythematosus, especially among those who are younger and newly diagnosed.
Dr. Garg and Dr. Petri both said that insurance does not automatically cover the costs of checking HCQ levels in the blood, which has been a consistent frustration in the field.
“Having more data validates the reason to do it,” Dr. Garg said.
She added that “HCQ blood levels are still not done routinely in all patients, and at times the test needs to be sent to outside laboratories.”