Feature

Measuring hydroxychloroquine blood levels could inform safe, optimal dosing


 

REPORTING FROM LUPUS 2019

The risk of retinopathy with 2 decades or more of hydroxychloroquine (Plaquenil) use for lupus is about 8%, and perhaps would be even less if doses were reduced when blood levels get above a certain level, according to an investigation of the Hopkins Lupus Cohort, an ongoing longitudinal study of lupus patients in the Baltimore area.

Dr. Michelle Petri

Dr. Michelle Petri

As innocuous as the assertions seem, they are anything but. They directly contradict a 2014 investigation from Kaiser Permanente that put the retinopathy risk after 20 years at almost 40%; that finding led directly to an American Academy of Ophthalmology recommendation to reduce the maximum hydroxychloroquine dose from 6.5 mg/kg per day ideal weight to 5 mg/kg real weight, where it remains to this day.

Meanwhile, very few rheumatologists have access to hydroxychloroquine (HCQ) blood levels because most commercial labs don’t offer them. Plasma testing is widely available, but it’s nowhere near as good, according to Michelle Petri, MD, a rheumatology professor at Johns Hopkins University, Baltimore; director of the Hopkins Lupus Cohort; and a respected authority on lupus management.

“The Kaiser Permanente study was very worrisome,” she said. “I remember that I thought it didn’t fit my practice at all; I don’t see 40%. It made me even more concerned when the ophthalmologists” reduced the dose, “because hydroxychloroquine is the most important medicine I have for my lupus patients; it is the only one that improves survival. We don’t want to scare our patients into thinking that 40% of them are going to have retinopathy.”

Dueling studies

Dr. Petri’s concerns led her and her team to launch their own investigation; they followed 537 Baltimore cohort members on HCQ as they went through eye exams by Hopkins retinopathy specialists, often with optical coherence tomography (OCT). With a sensitivity of 93% and specificity of 84%, OCT is the best screening method available.

“We found that the risk of retinopathy is not nearly as high as Kaiser Permanente found,” just 11.46% (11/96) with 16-20 years of use, and 8% (6/75) with 21 or more years. On average, “the risk is probably about 10% after 16 or more years, not 40%,” Dr. Petri said at an international congress on systemic lupus erythematosus.

Patients with “possible” retinopathy were not included in the analysis.

When asked for comment, Ronald Melles, MD, a Kaiser ophthalmologist in Redwood City, Calif.; one of the two authors on the Kaiser study; and an author on the subsequent AAO recommendations, stood by his work.

“A rate of 12% retinopathy after 16 years of use ... seems right in line with what we found.” However, “the fact that the rate went down to 8%” after 20 years does not make sense; “the longer you are on the medicine, the more likely you would be to develop the toxicity,” he said.

Maybe the fluctuation had to do with the fact that there were only 75 patients in the Hopkins study on HCQ past 20 years, whereas “we looked at 2,361 patients, and 238 were on the medication for” 20 years or more. Patients over 5.0 mg/kg per day had a 5.67-fold higher risk”of retinopathy, he said (univariate analysis, P less than .001).

Dr. Petri wasn’t buying it. The across the board recommendation was made “without any recognition that if you reduce the dose, you reduce the benefit,” she said.

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