Identification of new risk factors for hydroxychloroquine and chloroquine retinopathy in systemic lupus erythematosus patients

• Published in: Seminars in arthritis and rheumatism Vol. 66; p. 152417
• Main Authors: Trefond, Ludovic, Lhote, Raphael, Mathian, Alexis, de Chambrun, Marc Pineton, Pha, Micheline, Hie, Miguel, Miyara, Makoto, Papo, Matthias, Moyon, Quentin, Taieb, Dov, Saade, Sonia, Salem, Thouraya Ben, Haroche, Julien, Chasset, François, Aubart, Fleur Cohen, Zahr, Noël, Amoura, Zahir
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Adult; Antimalarials - adverse effects; Antimalarials - therapeutic use; Antirheumatic Agents - adverse effects; Case-Control Studies; Chloroquine; Chloroquine - adverse effects; Chloroquine - therapeutic use; Female; Humans; Hydroxychloroquine; Hydroxychloroquine - adverse effects; Hydroxychloroquine - therapeutic use; Lupus Erythematosus, Systemic - chemically induced; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - drug therapy; Male; Middle Aged; Retinal Diseases - chemically induced; Retinopathy; Risk Factors; Systemic lupus erythematosus; Systemic lupus erythematosus; Hydroxychloroquine; Retinopathy; Chloroquine
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2024.152417

Long-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3–8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney disease, concurrent tamoxifen therapy and pre-existing retinal or macular disease. However, those factors cannot explain the entire risk of developing antimalarial retinopathy. This study was undertaken to identify new risk factors associated with HCQ or CQ retinopathy (QRNP) in systemic lupus erythematosus (SLE) patients. This case–control (1:2) study compared SLE patients with QRNP (cases) to those without (controls). Controls were matched for sex and known QRNP risk factors: HCQ and/or CQ treatment duration (±1 year) and age (±5 year) at SLE diagnosis. Forty-eight cases were compared to 96 SLE controls. Multivariable logistic-regression analysis retained the following as independent determinants significantly associated with QRNP: concomitant selective serotonin-reuptake inhibitor (SSRI) or serotonin- and norepinephrine-reuptake inhibitor (SNRI) intake (OR [95 % confidence interval] 6.6 [1.2 to 40.9]; p < 0.01); antiphospholipid syndrome (OR=8.9 [2.2 to 41.4] p < 0.01); blood hydroxychloroquine/desethylchloroquine concentration ([HCQ]/[DCQ]) ratio <7.2 (OR 8.4 [2.7 to 30.8]; p < 0.01) or skin phototype ≥4 (OR 5.5 [1.4 to 26.5]; p = 0.02), but not daily HCQ dose, blood [HCQ] or body mass index. The results of this case–control study identified blood [HCQ]/[DCQ] ratio, concurrent SSRI/SNRI therapy, skin phototype ≥4 and antiphospholipid syndrome as new risk factors for QRNP. [Display omitted]