Ab1393 Hydroxychloroquine (Hcq) Blood Level as an Additional Risk Factor in Patients With a High Risk of Developing HCQ Retinopathy in the Asian Population: A Case-Control Study in a Tertiary Center

Background: Hydroxychloroquine retinopathy (HCQR) is an uncommon but severe complication resulting from the prolonged use of hydroxychloroquine (HCQ). The most predictive risk factors for HCQR are still not clearly understood, with a particular lack of comprehensive studies in Asian populations. Objectives: This study aims to identify risk factors associated with HCQR in autoimmune disease patients who have been exposed to HCQ for prolonged periods. Methods: In this single-center case-control study, participants were selected based on specific criteria: minimum three years of HCQ use, a daily HCQ dose of 400 mg, and undergoing at least one ophthalmologic examination for HCQR. Diagnosis of "definite HCQR" was determined by a retinal specialist according to 2020 guidelines from The Royal College of Ophthalmologists, UK. Additionally, blood levels of HCQ and its metabolites in patients were determined by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The study involved 76 participants, comprising 19 HCQR patients and 57 controls. Most patients were female (90.8%), with a median age of 50 years (interquartile range [IQR] 40-63) and median weight of 54 kg (IQR 48-62). The median duration of HCQ exposure was 11.7 years (IQR 9.3-13.8), and the median cumulative dose was 1,599 g (IQR 1,311-1,950). Key variables, including age, weight, HCQ exposure duration, and cumulative dose were similar across both groups. However, HCQR patients showed higher white blood cell counts (p=0.039) and marginally higher estimated glomerular filtration rates (eGFR) (p=0.060). Notably, HCQR patients exhibited significantly higher levels of HCQ and desethylchloroquine (DCQ) (p=0.004 and p=0.028, respectively), with a greater proportion having HCQ blood levels exceeding 1,000 ng/mL (84% versus 44%, p=0.002) or 750 ng/mL (95% versus 68%, p=0.030) (Table 1). Univariate logistic regression identified significant correlations between HCQR and variables like height (OR 0.911, 95% CI 0.830-0.999), and HCQ blood level >1,000 ng/mL (OR 6.827, 95% CI 1.788-26.059). Multivariate logistic regression, adjusted for confounders, retained the significance of HCQ blood level > 1,000 ng/mL (Adjusted OR 5.965, 95% CI 1.482-24.009) (Table 2). Conclusion: In Asian patients at high risk for HCQR due to long-term exposure and higher doses of HCQ, HCQ blood level greater than 1,000 ng/mL appears to be an additional risk factor. These findings provide crucial insights for the management and monitoring of patients on prolonged HCQ therapy. Table 1. Characteristic of patients according to the result of HCQR and the level of HCQ Table 2. Univariate and multivariate logistic regression analyses REFERENCES: [1] Yusuf IH et al. The Royal College of Ophthalmologists recommendations on monitoring for hydroxychloroquine and chloroquine users in the United Kingdom (2020 revision): executive summary. Eye (Lond). 2021 Jun;35(6):1532-1537. [2] Füzéry AK et al. A rapid and reliable method for the quantitation of hydroxychloroquine in serum using turbulent flow liquid chromatography-tandem mass spectrometry. Clin Chim Acta. 2013 Jun 5;421:79-84. Acknowledgements: NIL. Disclosure of Interests: None declared.