Retina screening rate in patients receiving hydroxychloroquine ‘remains low’
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Key takeaways:
- Hydroxychloroquine dosing averages in patients with lupus fall in line with AAO-prescribed standards.
- The rate of retina screenings should increase.
Although the annual retinopathy screening rate in patients with lupus receiving hydroxychloroquine has increased from 3.5% in 2006 to 22.5% in 2019, more work is needed to raise awareness, according to data from a South Korean study.
“Although [hydroxychloroquine (HCQ)] has remained the treatment option for SLE for over half a century, the prevalence of retinopathy, a rare but serious adverse event, has been reported,” Jae-Eun Lee, of the College of Pharmacy at Chung-Ang University, in Seoul, and colleagues wrote. “To reduce the retinal toxicity of HCQ, the American Academy of Ophthalmology (AAO) revised its guidelines twice.”
To investigate the relationship between hydroxychloroquine dosing and retinopathy screenings in patients receiving the drug for systemic lupus erythematosus, Lee and colleagues analyzed 2004 to 2019 data from the National Health Insurance Database in South Korea. The collected data included patient demographics as well as diagnostic codes and prescription information. Patients were included in the analysis if they were diagnosed with SLE at least one time between 2004 and 2019.
The researchers assessed patients’ sex, age and comorbidities to identify patterns of hydroxychloroquine use. In addition, they accounted for changing prescription doses by analyzing prescriptions and logged weight information from patients. For those who did not have weight information available for a given year, data were used from the next closest appointment, which was within 1 year of prescription due to South Korea’s health screening rules. Lee and colleagues accounted for primary retina screening tests and any other tests recommended by the American Academy of Ophthalmology.
The analysis included 38,973 patients with SLE, of whom 72.9% were prescribed hydroxychloroquine between 2004 and 2019. The percentage of patients prescribed hydroxychloroquine increased from 63% in 2004 to 76% in 2019, according to the researchers. The median daily dose of hydroxychloroquine per actual body weight changed from 5.88 mg per kg in 2004 to 3.98 mg per kg in 2019. In new users, the median daily dose changed from 5.45 mg per kg to 4.17 mg per kg.
Meanwhile, annual rates of retina screenings increased from 3.5% among new hydroxychloroquine users in 2006 to 22.5% in 2019, according to the researchers.
“We found that HCQ dosing management was adequate based on the revised AAO guidelines for HCQ in patients with SLE in Korea,” Lee and colleagues wrote. “However, despite a recent increase, the rate of implemented retinal screening tests remains low considering recommendations in the guidelines. It suggests the need to enhance awareness of retinal screening in clinical settings.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Ophthalmologic spectral-domain optical coherence tomography screening is the standard of care for monitoring hydroxychloroquine retinal toxicity. Screening is typically done annually. Recently, monitoring the hydroxychloroquine blood level itself has been recommended, as the prescribed hydroxychloroquine dose does not predict blood levels.
Several adverse cardiac effects of hydroxychloroquine use have been recognized, including a lengthening of the corrected QT interval (QTc), particularly in association with other medications that also lengthen the QTc, as well as the occurrence of hydroxychloroquine-induced cardiomyopathy. The antimalaria drugs chloroquine and hydroxychloroquine, and the commonly used macrolide antibiotic azithromycin are all known to increase the QTc. A QTc greater than 500 ms increases the risk for Torsade de Pointes (TdP) by 2- to 3-fold.
A report on patients with COVID-19 treated with chloroquine or hydroxychloroquine, with or without azithromycin, revealed no instances of TdP or arrhythmogenic death. Although the use of these medications resulted in QT prolongation, clinicians seldom needed to discontinue therapy. The risk for QT prolongation and TdP with hydroxychloroquine is limited to a series of case reports in patients with either chronic use or overdose, and most of these cases occurred with malaria or COVID-19, where the patient was severely ill.
Healthy patients taking chloroquine or hydroxychloroquine for malaria prophylaxis have not shown any cardiac effects, and studies in lupus and rheumatoid arthritis have shown fewer major adverse cardiac events than placebo.
Cardiomyopathy is a rare complication of prolonged hydroxychloroquine treatment. Antimalarial-related cardiotoxicity most commonly manifests clinically as a diffusely thickened, restrictive or dilated cardiomyopathy, or with conduction system abnormalities including atrioventricular block and bundle branch block. The mechanism of cardiotoxicity is still unclear. Biopsies reveal myocardium with degenerative changes and numerous lamellar body inclusions. It has been reported that cardiac function can recover after the early cessation of the drug.
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