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.