Background: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus and is often used for other inflammatory conditions, but a critical long-term adverse effect is vision-threatening retinopathy. Aim: To characterize the long-term risk of incident hydroxychloroquine retinopathy and examine the extent to which the average dose of hydroxychloroquine within the first 5 years of treatment predicts this risk. Design: Cohort study. Around: US Integrated Health Network Participants: All patients aged 18 years or older who received hydroxychloroquine for 5 years or more between 2004 and 2020 and underwent guideline-recommended serial retinopathy screening. Measurements: Hydroxychloroquine dosage was assessed from pharmacy dispensing records. Incident hydroxychloroquine retinopathy was assessed by central adjudication of spectral domain optical coherence tomography with assessment of severity (mild, moderate, or severe). The risk of hydroxychloroquine retinopathy was estimated over 15 years of use by weight-based hydroxychloroquine dose (>6, 5 to 6, or ≤5 mg/kg per day) using the Kaplan-Meier estimator. Results: Among 3,325 patients in the primary study population, 81 developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively. The cumulative incidences of retinopathy at 15 years were 21.6% for doses greater than 6 mg/kg per day, 11.4% for 5 to 6 mg/kg per day, and 2.7% for doses of 5 mg/kg per day or less. The corresponding risks of moderate-to-severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively. Limitation: Possible dose misclassifications due to non-compliance with filled prescriptions. Conclusion: In this large contemporary cohort with active surveillance retinopathy screening, the overall risk of hydroxychloroquine retinopathy was 8.6% after 15 years, and most cases were mild. The highest dose of hydroxychloroquine was associated with a progressively increased risk of incident retinopathy. Main funding source: National Institutes of Health. |
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Long-term use of low-dose hydroxychloroquine associated with low risk of retinopathy
A cohort study of more than 3,000 people receiving hydroxychloroquine for 5 years or more with guideline-recommended serial retinopathy screening found that the overall risk of incident retinopathy was low, and most documented cases were mild. The highest dose of hydroxychloroquine was associated with a progressively higher risk. The findings are published in Annals of Internal Medicine .
Hydroxychloroquine is recommended for patients with systemic lupus erythematosus and some other inflammatory conditions, but vision-threatening retinopathy is a serious long-term adverse effect. Guidelines recommend keeping the dose at 5 mg/kg body weight per day or less. However, the available study evidence supporting this is relatively weak.
Researchers from Kaiser Permanente Northern California and Harvard Medical School studied 3,325 people who received hydroxychloroquine for 5 years or more between 2004 and 2020 to characterize the long-term risk of incident hydroxychloroquine retinopathy and examine the extent to which the average hydroxychloroquine dose in the first 5 years of treatment predicts this risk. The researchers used medical and pharmacy records to analyze hydroxychloroquine dosing and reviewed annual optical scans over time to determine if there was evidence of retinopathy.
If cases of retinopathy were identified, they were classified as mild, moderate, or severe. The researchers then calculated the risk of developing retinopathy after 15 years based on the average dosage levels during the first 5 years.
They found that 81 participants developed hydroxychloroquine retinopathy with overall cumulative incidences of 2.5 and 8.6 percent after 10 and 15 years, respectively, and the risk was higher for those who received a higher dose during the first 5 years of treatment. Researchers note that regular screening can identify this problem at an early, treatable stage.
