Hydroxychloroquine for Rheumatic Disease Not Linked to QTc Prolongation

November 18, 2020
Kenneth Bender, PharmD, MA

Patients with SLE or RA had comparable mean QTc length, regardless of whether or not they received hydroxychloroquine treatment

Hydroxychloroquine (HCQ) was not associated with QTc prolongation in patients receiving it for systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), in a large cohort study reported at the American College of Rheumatology (ACR) 2020 Virtual Meeting.

HCQ is a cornerstone therapy for SLE, and is used either as monotherapy or in combination with other disease-modifying antirheumatic drugs (DMARDs) for RA, Elizabeth Park, MD, a fellow in Rheumatology at the Columbia University Vagelos College of Physicians and Surgeon, and colleagues noted.

"However, its use in the treatment of COVID-19 has raised concerns for the possibility of QTc prolongation and development of arrhythmia," Park and colleagues observed.

To ascertain the relevance of those concerns to its use in treating patients for SLE or RA, Park and colleagues conducted a study involving 681 patients without cardiovascular disease, comprising 2 prospective RA cohorts with EKGs as part of study data collection (n = 307) and one retrospective SLE cohort (n = 374) with EKG performed as part of standard of care.

Regression models were used to analyze association between QTc length and HCQ use, adjusted for disease-specific characteristics and cardiovascular disease risk factors.

"For the SLE cohort, we retrospectively reviewed QTc length and HCQ use, at the time of the EKG, from an electronic medical records system," Park explained to HCPLive®. "For the RA cohorts, the EKG was obtained at the time of cardiac imaging, and HCQ use was assessed at the time of EKG."

The investigators found that in the entire cohort, adjusted QTc length in HCQ users was comparable to that of non-HCQ users; with multivariate logistic modeling demonstrating that HCQ use was not a significant predictor of prolonged QTc >440 or >500ms (OR, 0.89; 95% CI, 0.25-3.2 and OR, 0.11; 95% CI, 0.007-1.7, respectively). HCQ was also not found to be a predictor of prolongation in either the RA of SLE separate cohorts.

Although 9 of 11 SLE patients with a QTc >500 were on HCQ, this was too small a number to detect statistically significant differences between the HCQ groups The investigators noted that there were no arrhythmia or deaths associated with QTc >500ms.

There were no significant interactions between HCQ use and other QTc prolonging medications in the entire cohort, but there was a significant interaction (P = .014) between HCQ use and antipsychotic use in the SLE cohort, with longer QTc for those on both medications than those only on HCQ.

"Although we did not find a statistical interaction between HCQ use and other QTc prolonging medications, there were several things we did not include in the analysis which could alter the conclusions/interpretation," Park commented. "That includes length of HCQ therapy, dose and level of HCQ, and adherence to HCQ—all of which could affect cumulative exposure. Also, length, dose, and adherence to each QTc prolonging medication was also not assessed.”

Park acknowledged that the exclusion of patients with symptomatic cardiovascular disease from the study precluded extrapolation of the findings to that population, but indicated her group is planning further study to explore the safety of HCQ in that high-risk group.

"That being said, one could make the case for those with known cardiac conduction abnormalities—or perhaps with other strong risk factors for QTc prolongation, or other QTc prolonging medications that cannot be stopped/dose reduced, elderly, etc.—to be cautious with dosing HCQ above the recommended guidelines, and consider EKG monitoring," Park advised.

The study, "Hydroxychloroquine Use Was Not Associated with QTc Length in a Large Cohort of SLE and RA patients," was presented at ACR 2020.