New Findings on Hydroxychloroquine, Denosumab

ACR Convergence 2020—At two plenary sessions, speakers highlighted key findings, including results on the QTc interval in patients on hydroxychloroquine, and data from a study on denosumab vs. alendronate for glucocorticoid-induced osteoporosis.

The QTc Interval & Hydroxychloroquine
The safety profile and optimal dosing of hydroxychloroquine has been a topic for decades because it is known to potentially result in long-term toxicities in the skin, retina and heart from long-term storage of metabolites. At the plenary session on Friday, Nov. 6, Elizabeth Park, MD, a rheumatology fellow at Columbia University Irving Medical Center, New York, discussed a study on an unresolved issue about its potential side effects: the possibility of prolonged QTc length as assessed by electrocardiogram (ECG).

Prolonged QTc length, potentially resulting from blockade of the inward cellular potassium current, has long been associated with the risk of abnormal heart rhythms that can lead to sudden cardiac death (such as torsades de pointes), although the exact length indicating true risk is a point of debate.¹ Several cohort studies have also found it a predictor of increased overall cardiovascular morbidity and mortality.² An association of increased QTc length with hydroxychloroquine use has been found in some previous medical reports, but not in others.^3–9

Dr. Park explained that interest in the topic heightened in recent months after an observational study of 90 patients hospitalized with COVID-19 found that 19% of patients who received hydroxychloroquine had a prolonged QTc of more than 500 ms, including one case of torsades de pointes. Those receiving hydroxychloroquine plus azithromycin (a drug thought to extend the QTc interval) had increased prolongation compared to those receiving only hydroxychloroquine.⁹

In their recent study, Dr. Park and colleagues examined two different rheumatoid arthritis (RA) cohorts (evaluated prospectively) and a cohort of patients with systemic lupus erythematosus (SLE, evaluated retrospectively), for a combined cohort of 530 patients. ECG information was assessed at the same time as hydroxychloroquine use, providing information from a single cross-sectional time point. They excluded potential participants with known cardiovascular disease.

Of their cohort, 93% of the patients with SLE were taking hydroxychloroquine, as were 24% of the RA patients (54% of the group as a whole).

Of the cohort, 44% had a QTc greater than or equal to 440; 7.5% demonstrated a QTc greater than or equal to 500. Dr. Park said, “This is significant, as prolonged QTc length—defined as greater than 450 in men and greater than 470 in women—independently predicts sudden cardiac death in the literature.” No cardiac arrhythmias or associated deaths occurred during the study period.