New insights into the long-term adverse effects of antimalarials in patients with systemic lupus erythematosus.

Abstract

Background: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE) because of its efficacy and safety. Previous studies of antimalarial toxicity under non-experimental conditions have often grouped hydroxychloroquine and chloroquine. This study focuses on the long-term toxicity of antimalarial drugs in SLE patients at a single reference centre. The research seeks to identify trends in antimalarial toxicity and determine risk factors contributing to long-term adverse effects.

Materials and methods: Retrospective data were collected from electronic medical records of consecutively diagnosed SLE patients, followed for at least 5 years, from 1998 to 2017. The outcome variable "antimalarial long-term adverse effect" was considered if the adverse effect occurred after at least 5 years of continuous antimalarial treatment. Hazard regression analysis was used to identify independent factors associated with long-term antimalarial adverse effects.

Results: Three hundred 22 patients followed for a median of 15 years were analysed. The mean age at SLE diagnosis was 33.4 years, and 91.3% were women. Antimalarial drugs were started in 314 (97.5%) patients. Adverse effects were observed in 55 (17.5%) patients, mainly macular toxicity (11.5%). The incidence of all types of toxicity was higher in the long-term users than in the short-term users (12.1% vs 5.4%; p < .001). Previous use of chloroquine (HR 3; 95%CI 1-9), anti-ß2-glycoprotein antibody positivity (HR 2; 95%CI 1-4) and hydroxychloroquine doses higher than 5 mg/kg/day (HR 2.6; 95%CI 1-7) were identified as independent factors associated with long-term antimalarial toxicity.

Conclusions: In our experience over the past 20 years, almost all SLE patients were treated with antimalarials. Macular toxicity was the most common long-term adverse effect. Patients with previous use of chloroquine, higher than recommended doses of hydroxychloroquine, and positive anti-ß2-glycoprotein antibodies were more likely to develop long-term antimalarial toxicity.