Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case–control study with hydroxychloroquine blood-level analysis

Abstract

Objective HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels. Methods This case–control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy. Results The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P < 0.001), height (P = 0.045), creatinine clearance (P < 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P < 0.001), higher cumulative HCQ dose (P < 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P < 0.0001, odds ratio 8.7) remained significantly associated with retinopathy. Conclusion SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.

Frequency and risk factors for hydroxychloroquine retinopathy among patients with systemic lupus erythematosus

“…Also, we found that the cumulative dose of the hydroxychloroquine therapy was significantly related to the hydroxychloroquine retinopathy that was in agreement with Petri et al [ 23 ] and Lenfant et al [ 11 ]. Previously, the cumulative dose was described as one of the risk factors of the hydroxychloroquine retinopathy [ 14 , 17 ].…”

“…In this study, weight-based daily dose was not a risk factor for HCQ retinopathy. However, the previous studies emphasized that the daily dose of more than 5 mg/kg is one of the most important risk factors for HCQ retinopathy [ 7 , 11 , 17 ]. The explanation might be that most of the studied patients’ weights were above 70 kg and most of them received 400 mg/day or less, also the low socioeconomic level of our patients might make them non-compliant to the treatment.…”

Reply

“…We agree with Dr. Yokogawa and colleagues that in the study by Lenfant et al (1), the lack of findings supporting a relationship between HCQ blood concentration and retinopathy may well have been due to the fact that Lenfant and colleagues selected an adherent control group, which likely inflated the average HCQ levels in their controls relative to typical patients.…”

“…HCQ blood levels were repeatedly measured prior to the onset of retinopathy in all patients. In contrast, the study by Lenfant et al was a case–control study, with cases and controls recruited from different sources, and in the controls, HCQ blood levels were measured only at a single time point (1).…”

Early‐Onset Hydroxychloroquine Retinopathy and a Possible Relationship to Blood Levels: Comment on the Article by Petri et al

“…Petri et al report that higher blood levels of hydroxychloroquine (HCQ) predicted development of HCQ retinopathy (1). However, in a recent case-control study, HCQ blood levels were not associated with retinopathy (2). The inconsistency may arise from dosage adjustment over time and the timing of blood level testing.…”