Higher dosing, duration of use intensifies risk for hydroxychloroquine retinopathy
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The risk for hydroxychloroquine retinopathy increases with higher dosing per actual and ideal body weight, and with longer duration of use, according to data presented at ACR Convergence 2021.
When hydroxychloroquine use causes mild retinopathy, people have no symptoms, and specialized screening tests, such as OCT, are needed to detect retinal damage, April M. Jorge, MD, of Massachusetts General Hospital in Boston, said during a virtual press conference, where she presented data from a prospective analysis of risk factors for hydroxychloroquine retinopathy and its subtypes.
“This condition is feared, because if it becomes more severe, then patients can develop vision loss,” Jorge said.
Stopping the medication is thought to likely prevent progression of retinopathy, and specialized screening for hydroxychloroquine retinopathy is recommended at least once a year for long-term users, she said.
“But an ongoing problem has been in identifying who is really at risk for developing hydroxychloroquine retinopathy, and what are the risk factors. There have been several other studies looking at the risk and risk factors of this complication. However, they have generally been smaller in size or had other limitations to the methodology,” Jorge said.
To determine the risk factors for hydroxychloroquine retinopathy, Jorge and colleagues conducted a nested case-control study within a large cohort of users from a U.S. integrated health network. The researchers included 4,899 individuals who used hydroxychloroquine for at least 5 years from 1997 to 2020 and assessed retinopathy based on spectral domain-OCT scans. All scans were reviewed by an ophthalmologist, while a second ophthalmologist examined all abnormal scans, as well as a random subset of normal scans. Discrepancies between the two were addressed through consensus.
Each scan was graded as mild, moderate or severe retinopathy, no retinopathy, or non-hydroxychloroquine retinopathy. Cases of retinopathy were further classified as having either a parafoveal or pericentral pattern. The researchers matched cases of hydroxychloroquine retinopathy with up to five control individuals based on age, sex and drug initiation year, using risk set sampling. Hydroxychloroquine use duration, cumulative dose, average daily dose, and dose per body weight were obtained through pharmacy records.
In all, 164 patients from the cohort had hydroxychloroquine retinopathy, 131 with a parafoveal pattern and 33 with pericentral pattern. Among these, 159 were matched to 755 control individuals.
The risk for hydroxychloroquine retinopathy doubled for every additional 5 years of use. In addition, cumulative dose was associated with an adjusted risk ratio of 4.28 (95% CI, 2.69-6.81) per additional 500 g, while dosing category per mg/kg of actual or ideal body weight strongly correlated with the risk for retinopathy, according to Jorge.
Patients of Asian ancestry had an overall increased risk for hydroxychloroquine retinopathy, as well as for a pericentral pattern “that might be harder to detect, particularly if it's not on the radar of the person doing the screening test,” Jorge said.
Chronic kidney disease was also associated with increased risk: a two times higher risk for overall retinopathy and a three times higher risk for moderate or severe retinopathy.
“The odds of developing hydroxychloroquine retinopathy really do increase with higher dose per body weight and with the longer duration of use,” Jorge said. “However, with regular screening studies, the majority of these cases are mild and therefore asymptomatic. Patients with some of the additional risk factors may need closer monitoring or perhaps dose adjustment. Overall, in order to optimize the care of our patients, the risks of hydroxychloroquine retinopathy need to be weighed against the benefits of this medication when choosing its optimal use for each patient.”
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Jorge A. Abstract 0989. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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