medwireNews: Higher hydroxychloroquine blood levels, along with older age, higher BMI, and longer duration of hydroxychloroquine use, are significantly associated with increased rates of hydroxychloroquine retinopathy, research shows.
Michelle Petri (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) and co-investigators say their study highlights for the first time “the utility of hydroxychloroquine blood levels in predicting retinopathy risk.”
Writing in Arthritis & Rheumatology, Petri and co-authors explain that, in 2016, following concerns about retinal toxicity, the American Academy of Ophthalmology reduced the recommended dose of hydroxychloroquine from 6.5 mg/kg to less than 5.0 mg/kg.
However, they say that the recommendations “were made without evidence that the lower dose of hydroxychloroquine would have the same efficacy for SLE [systemic lupus erythematosus] activity or the same protective role against cardiovascular risk factors and thrombosis.”
To investigate factors associated with the risk for hydroxychloroquine retinopathy, in 2013 Petri and team began repeatedly assessing 537 patients with SLE (92% women) for hydroxychloroquine blood levels and hydroxychloroquine retinopathy.
They report that the overall prevalence of confirmed retinopathy was 4.3% using fundus examination plus one or more additional retinal screening test (typically optical coherence tomography).
The rate of retinopathy increased significantly with age, from 0.5% among participants younger than 45 years, to 4.4% in those aged 45–59 years, and 10.1% in those aged 60 years and older.
The retinal toxicity rate also increased significantly with increasing BMI, from 2.0% among individuals with a BMI below 20 kg/m2 to 9.4% among those with a BMI of 35 kg/m2 or above.
The duration of hydroxychloroquine use among the cohort ranged from 0 to 48 years, and the researchers found that the risk for retinopathy increased significantly with increasing duration of use, peaking at 16–20 years.
Specifically, patients had a 1.0% risk for retinopathy in the first 5 years of hydroxychloroquine use, increasing to 1.8%, 3.3%, and 11.5% during years 6–10, 11–15, and 16–20, respectively, then falling to 8.0% after 21 years of use.
Furthermore, the researchers report that the risk for retinopathy increased significantly with increasing mean and maximum hydroxychloroquine blood levels. For example, the risks were 1.2% versus 7.9% for individuals in the lowest and highest tertiles of mean hydroxychloroquine level, and 1.2% versus 6.7% for those in the lowest and highest tertiles of maximum hydroxychloroquine level.
The authors therefore conclude that hydroxychloroquine blood level monitoring could be used “to reduce over-dosage.”
They add: “Although both the mean and maximum blood levels predict risk, we believe mean blood levels provide a better measure than maximum level to assess risk due to the issues of patient non-adherence and due to the variation we observed even when the patient is adherent.”
By Laura Cowen
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