Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety

Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common than previously thought. Adhering to careful weight-based dosing can significantly reduce the risk of this adverse event and is recommended in recent guidelines. We used electronic health record data from a large health system to examine HCQ dosing over a 5-year period and identify risk factors associated with higher dosage of HCQ. We constructed a longitudinal, retrospective cohort of patients with HCQ prescriptions (1681 patients with 3490 prescribing events) between 2012 and 2016. We measured HCQ dosing patterns relative to guidelines (<6.5 and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects logistic regression to identify sociodemographic, clinical and health system factors associated with receiving higher than recommended doses of HCQ. The proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012 to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg fell from 38% in 2012 to 30% in 2016. Low body weight (<68 kg) was strongly associated with receiving doses of HCQ above 6.5 mg/kg across all time points, even after adjusting for other factors (odds ratios ranging from 13.2 to 21.0). Although the proportion of patients receiving higher than recommended HCQ doses has declined over a period of 5 years, a substantial number of individuals remain at increased risk for toxicity. Given the widespread use of HCQ in immune-mediated diseases, our study suggests that interventions aimed to ensure appropriate dosing are warranted to improve patient safety.