A new referee: blood levels
Dr. Petri and her team also found that HCQ blood levels correlated with retinopathy, and it was a direct relationship. Patients in the highest maximum tertile (1,753-6,281 ng/mL) had a retinopathy rate of 6.7%, a good deal higher than patients in lower tertiles. It was the same story with the highest mean tertile (1,117-3,513 ng/mL). Retinopathy in that group occurred in 7.9% versus 3.7% or less in lower tertiles. The findings were statistically significant.
Patients in the third tertile “are at the greatest risk, so I reduce their dose,” but “I do not want to reduce the dose across the board” to 5 mg/kg per day; that’s overreach. The tertile approach, if it pans out, might be a better way, she said.
The problem with plasma levels is that HCQ binds to red blood cells, so plasma levels are artificially low and do not indicate the true HCQ load. For now, just one company in the United States offers HCQ blood levels: Exagen.
“We have to get the big companies to start offering” this, and “I want rheumatologists to adopt it. I am lucky at Hopkins [because] we have our own homegrown blood level assay,” she said.
Dr. Melles agreed that tracking blood level makes sense, “but the literature I am aware of has not been able to closely correlate either lupus disease activity or retinal toxicity with blood levels. Also, we have seen some patients at lower doses develop toxicity and other patients on higher doses without any detectable changes.”
Still, “we would like to see [this] studied more, perhaps with newer analytic methods,” said his coauthor on the Kaiser study, and also the lead author on the AAO guidelines, Michael Marmor, MD, professor emeritus of ophthalmology at Stanford (Calif.) University.
In the end, on the same team
Dr. Petri said there is interest among some of her fellow members of the American College of Rheumatology to work with AAO to revise the guidelines. “Until then,” she said, “I want the ophthalmologists to withdraw” them.
She’s worried about undertreatment and believes that the previous AAO guideline, up to 6.5 mg/kg per day ideal weight, was fine, “with some understanding that there are high-risk groups, such as the elderly and people with renal impairment, where the dose should be reduced.”
“No matter how obese a patient is, I cap it at 400 mg/day,” she said, and, with the luxury of HCQ blood level testing, “no matter the weight, if the person is in the upper tertile, I reduce the dose.”
Dr. Michael Marmor
Dr. Marmor agreed that “if rheumatologists prescribe 5 mg/kg real weight and do not stress compliance, some patients may indeed be underdosed.”
“However, that is a fault of the doctor and patient relationship,” he said, “not the guideline; we do not feel it ethical to prescribe higher doses which could increase toxicity in reliable patients ... just because some patients might be unreliable.”
Overall, “I have not heard complaints from rheumatologists in our area, who try hard to follow the current recommendations. ... any doctor can use the dose he or she feels is necessary for a patient. Several recent reports [also] suggest the incidence of toxicity is falling now with usage of AAO guidelines, [and] I am not aware of any data” showing that management has become less effective, he said.
In the meantime, “I assure you that AAO wants ... to serve both specialties, and will change the guidelines when there is new, defensible data,” he added.
The Hopkins team found that the risk of HCQ retinopathy was highest in men and white patients, as well as older people. Body mass index and hypertension also predicted retina issues.
“As screening tests are frequently abnormal due to causes other than HCQ ... stopping [it] based on an abnormal test without confirmation from a retinopathy expert could needlessly deprive an SLE patient of an important medication,” they said.
The Hopkins Lupus Cohort is funded by the National Institutes of Health. The physicians didn’t have any relevant disclosures.
SOURCES: Petri M et al. Lupus Sci Med. 2019;6(suppl 1). Abstracts 15 and 16.