A blood-level reference range of 750-1200 ng/mL of hydroxychloroquine (HCQ) has been linked with 71% lower odds of active lupus, new research suggests.
Researchers, led by Shivani Garg, MD, assistant professor of rheumatology at the University of Wisconsin, taking hydrochlorothiazide with sulfa allergy 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 September 4 in Arthritis Care & Research, could help clinicians personalize HCQ doses to maximize efficacy for each patient.
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, seven (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 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/d, and the American Academy of Ophthalmology followed with guidelines for HCQ retinopathy screening that recommended reducing HCQ to ≤ 5 mg/kg/d.
Petri said that the range 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 ≥ 1068 ng/mL vs those with levels < 648 ng/mL (relative risk, 0.31; 95% CI, 0.11-0.86; P = .024).
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, Garg told Medscape Medical News.
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.
Garg and 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,” 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.”
Importance for Patients With CKD
Many patient factors can affect how the body absorbs HCQ, Garg said, so finding the right level that is safe and maximizes benefit individually is important.
The findings are particularly important for patients with chronic kidney disease (CKD) of stage 3 or higher, Garg said.
The authors write that because kidneys clear more than half of all HCQ, impaired kidney function could boost HCQ blood levels, risking toxicity.
“Our study found a sixfold higher odds of having supratherapeutic HCQ blood levels in patients with CKD stage ≥3,” they write.
Garg added that if blood levels cannot be analyzed in all patients, they could be prioritized in patients with CKD stage 3 or above because these patients are at “higher risk of being underdosed with arbitrary reductions in HCQ doses and carry higher risk of toxicity if HCQ doses are not adjusted.”
More research will uncover other high-risk groups who would benefit most from close monitoring of HCQ blood levels, she said.
The study was supported by an award from the University of Wisconsin, Madison, and by an award to the institution from the National Institutes of Health National Center for Advancing Translational Sciences. Garg and co-authors as well as Petri report no relevant financial relationships.
Arthritis Care Res. Published online September 4. Abstract
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @MLfrellick
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