Nationwide patterns of hydroxychloroquine dosing and monitoring of retinal toxicity in patients with systemic lupus erythematous

초록

Background: Hydroxychloroquine (HCQ) is commonly used in systemic lupus erythematous (SLE), however rare but severe retinal toxicity associated its long-term use have been reported. To minimize the risk of HCQ retinopathy, the American Academy of Ophthalmology (AAO) revised practice guidelines twice, limiting the recommended dose to <6.5 mg/kg IBW in 2011 and <5.0 mg/kg ABW in 2016. In addition, AAO guidelines recommend regular ophthalmologic screening at baseline and annually after 5 years of HCQ use with modern screening methods such as automated visual field assessment or spectral-domain optical coherence tomography. Objective: To identify the temporal trends in HCQ prescriptions and screening of retinopathy in patients with SLE according to update of clinical guidelines, and to describe the prevalence of visual impairment in patients who were prescribed HCQ. Methods: We used data of patients with diagnosis of SLE (ICD10, M32) between 2004 and 2019 from the National Health Insurance Service in Korea. To measure HCQ dosing patterns, we used 2 formulas based on ideal or actual body weight and we identified daily dose trends before and after the point of AAO guideline changes. We also evaluated the implementation rate of retinal screening according to update of the AAO guidelines. In addition, we identified patients who were diagnosed with visual impairment (ICD10, H53 or H54) between 2007 and 2019 after using HCQ, and assessed patterns of HCQ dosing, duration, and retinal screening before diagnosis of visual impairment. Results: Among 249,897 patients with SLE, 183,541 (73.4%) were prescribed HCQ during the study period. Median daily dose of HCQ was decreased from 5.97mg /kg ABW in 2004 to 4.04mg /kg ABW in 2019. The implementation rate of modern retinal screening modalities was increased significantly from 4.34% in 2004 to 26.33% in 2019. Among patients with SLE using HCQ, 4,293 (2.3%) patients were diagnosed with visual impairment; their median daily dose before diagnosed the visual impairment was 4.97 mg/kg ABW. Conclusion: From 2004 to 2019, prescribing dose continued to decline, falling below the recommended dose in the guidelines (<5.0 mg/kg ABW/day). In addition, the screening implementation rate increased steadily and especially in recommended screening modalities during the same period. The prevalence of vision impairment was similar to previously reported prevalence of HCQ retinal toxicity (1.6% to 6.3%), and further research assessing risk factors of HCQ retinopathy is needed.