Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case–control study with hydroxychloroquine blood-level analysis
Tiphaine Lenfant, Sawsen Salah, Gaëlle Leroux, Elodie Bousquet, Véronique Le Guern, François Chasset, Camille Françès, Nathalie Morel, J. Chezel, T. Papo, P. Cacoub, Luc Mouthon, G. Guettrot-Imbert, Pascal Cohen, Alexis Régent, Martine Mauget‐Faÿsse, Jean‐Charles Piette, M. Jallouli, N. Costedoat‐Chalumeau, PLUS Group, Félix Ackermann, Zahir Amoura, Bouchra Asli, L. Astudillo, O. Aumaître, C. Bélizna, Nadia Belmatoug, Olivier Benvéniste, A. Benyamine, Holly Bezanahary, Benoı̂t Blanchet, Patrick Blanco, O Blétry, Bahram Bodaghi, Pierre Bourgeois, B. Brihaye, Emmanuel Chatelus, Judith Cohen‐Bittan, R. Damade, Éric Daugas, C. Degennes, Jean‐François Delfraissy, C. Delluc, Aurélien Delluc, H. Desmurs‐Clavel, P. Duhaut, Alain Dupuy, I. Durieu, E A Hang-Korng, Olivier Fain, Dominique Farge, Christian Funck‐Brentano, Lionel Galicier, Frédérique Gandjbakhch, Justine Gellen‐Dautremer, Pascale Ghillani‐Dalbin, Bertrand Godeau, Cécile Goujard, C. Grandpeix, C. Grangé, Lamiae Grimaldi‐Bensouda, Loïc Guillevin, É. Hachulla, Jean-Robert Harlé, Julien Haroche, Pierre Hausfater, J-S Hulot, Jean Jouquan, Gilles Kaplanski, Homa Keshtmand, Jean‐Emmanuel Kahn, Mehdi Khellaf, Olivier Lambotte, David Launay, D. Lê Thi Huong, Philippe Lechat, H. Lévesque, Olivier Lidove, Frédéric Lioté, Eric Liozon, L Y Kim, Matthieu Mahévas, K. Mariampillai, Xavier Mariette, Alexis Mathian, K. Mazodier, Marc Michel, Lucile Musset, Rokiya Ngack, J. Ninet, Éric Oksenhendler, Jean‐Luc Pellegrin, L. Pérard, Olivier Peyr, Anne‐Marie Piette, Vincent Poindron, Jacques Pourrat, Fabienne Roux, David Saadoun, Karim Sacré
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.