ATLANTA -- New research presented at ACR Convergence, the American College of Rheumatology's annual meeting, discovers that use of hydroxychloroquine, a generic drug, does not cause any significant differences in QTc length or prolonged QTc, key measures of heart rate, in people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (ABSTRACT #0431).
Rheumatoid arthritis is the most common type of autoimmune arthritis. It is caused when the immune system (the body's defense system) is not working properly. RA causes pain and swelling in the wrist and small joints of the hand and feet. SLE is a chronic disease that causes systemic inflammation which affects multiple organs.
Hydroxychloroquine is a cornerstone treatment for SLE, and patients with RA may also take the drug either alone or in combination with other treatments. However, there are concerns about its possible heart-related side effects: the prolongation of QTc, or the time span the heart takes to contract and relax, and the development of arrhythmia (irregular heartbeats). This new study assessed QTc lengths in patients with RA and SLE and its association with hydroxychloroquine use.
"Hydroxychloroquine remains the foundation of disease-modifying antirheumatic drug therapy in rheumatic disease patients. Given recent concerns surrounding hydroxychloroquine's use in COVID-19 patients and subsequent arrhythmic events, we wanted to examine the associations between its use and the QTc length on electrocardiograms in a large, asymptomatic cohort of RA and SLE patients," says study co-author Elizabeth Park, MD, Rheumatology Fellow at Columbia University Irving Medical Center.
The study analyzed data on 681 RA and SLE patients without clinical cardiovascular disease, including two prospective RA cohorts of 307 patients and a retrospective SLE cohort of 374patients, that included electrocardiogram (EKG) results. The researchers explored the association between QTc length and hydroxychloroquine use by these patients, and they adjusted the data for disease-specific characteristics and cardiovascular disease (CVD) risk factors. Of the whole study group (RA and SLE), 54% used hydroxychloroquine and 44% had QTc lengths of more than 440 milliseconds. They found that the adjusted QTc length among hydroxychloroquine users was comparable to those who did not use the drug.
Their results also showed that hydroxychloroquine use did not significantly predict prolonged QTc for either the whole cohort or the RA and SLE patient cohorts. However, nine out of 11 of the SLE patients who did have a prolonged QTc were taking hydroxychloroquine. Yet these observations were too small to detect statistically significant differences between the hydroxychloroquine groups.
Prolonged QTc, or more than 500 milliseconds, was not associated with arrhythmias or deaths among these patients. The study also did not find any significant interactions between hydroxychloroquine and other QTc-prolonging medications in the patients. Hydroxychloroquine use combined with other QTc-prolonging medications resulted in a comparable QTc interval to hydroxychloroquine alone. In the SLE group, hydroxychloroquine combined with anti-psychotic drugs did result in longer QTc compared to using hydroxychloroquine alone, however.
"Overall, the use of hydroxychloroquine did not predict QTc length, even while adjusting for critical confounding factors, namely the use of other QTc-prolonging medications," says Dr. Park. "Our findings reinforce the fact that hydroxychloroquine remains a safe, effective long-term disease-modifying drug for our rheumatic disease patients. It's important to remember that COVID-19 patients who received hydroxychloroquine were likely critically ill. Therefore, the effect of COVID-19 itself on the heart and subsequent arrhythmia must be considered. They also likely concurrently received azithromycin, another QTc-prolonging medication. Our next steps are to stratify data by length and cumulative dose of hydroxychloroquine therapy and analyze the associations with QTc length."
This research was supported by funding from the Rheumatology Research Foundation.
About ACR Convergence
ACR Convergence, the ACR's annual meeting, is where rheumatology meets to collaborate, celebrate, congregate, and learn. Join ACR for an all-encompassing experience designed for the entire rheumatology community. ACR Convergence is not just another meeting - it's where inspiration and opportunity unite to create an unmatched educational experience. For more information about the meeting, visit https://www.rheumatology.org/Annual-Meeting, or join the conversation on Twitter by following the official hashtag (#ACR20).
About the American College of Rheumatology
The American College of Rheumatology (ACR) is an international medical society representing over 7,700 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.
Hydroxychloroquine Use Was Not Associated with QTc Length in a Large Cohort of SLE and RA Patients
Hydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and is used as monotherapy and combined with other DMARDs in rheumatoid arthritis (RA). However, its use in the treatment of COVID-19 has raised concerns for the possibility of QTc prolongation and development of arrhythmia. We therefore assessed QTc length in a large SLE and RA cohort and its association with HCQ use.
A total of 681 SLE and RA patients without clinical cardiovascular disease (CVD) were analyzed from two prospective RA cohorts with EKGs as part of study data collection (n=307), and one retrospective SLE cohort (n=374) with EKGs performed as part of standard of care. The participants from all three cohorts were recruited from tertiary referral centers. The association between QTc length and HCQ use was explored in regression models and adjusted for disease-specific characteristics and CVD risk factors.
Of the entire (SLE+RA) cohort, 54% were HCQ users and 44% had a QTc > 440 ms. The mean QTc length was 437± 28 ms. In the entire cohort, adjusted QTc length in HCQ users was comparable to that of non-HCQ users (Figure 1). In multivariate logistic modeling, HCQ use was not a significant predictor of prolonged QTc > 440 or >500 ms for the entire cohort (OR 0.89; CI 0.25-3.2, & OR 0.11; CI 0.007-1.7, respectively), nor for the RA cohort (OR 1.1; CI 0.54-2.2, & OR 0.80; CI 0.23-2.8, respectively). HCQ use was not a significant predictor of a QTc >440 ms in the SLE subset (OR 2.0; CI 0.46-8.8). However, 9/11 SLE patients with a QTc >500 ms were on HCQ, yet these observations were too small to detect statistically significant differences between the HCQ groups. Importantly, QTc >500 ms was not associated with arrhythmias or deaths. No significant interactions were found between HCQ use and other QTc prolonging medications in the entire cohort. In fact, use of HCQ combined with any QTc prolonging medication was associated with a comparable QTc length (434 ms; CI 430-439) vs. use of HCQ alone (433 ms; CI 429-437). A significant interaction (p=0.014) was found between HCQ use and antipsychotic use in the SLE cohort, with QTc length being longer (441 ms; CI 428-454) for those on both vs. those only on HCQ (432 ms; CI 428-436).
This study demonstrates that in a large combined cohort of SLE and RA patients, QTc length does not significantly differ in HCQ users compared with non-HCQ users even while adjusting for potential clinical confounders. Importantly, HCQ use was not associated with a prolonged QTc ( >440 ms) in the combined and individual SLE and RA cohorts, nor was HCQ use a significant predictor of QTc length.