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Treatment of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) with hydroxychloroquine (HCQ) has not been associated with prolongation of the QTc interval, a researcher reported at the annual virtual meeting of the American College of Rheumatology.
In a multivariate logistic analysis of three cohorts, totaling nearly 700 patients, HCQ use was not a significant predictor of prolonged QTc greater than 440 ms (OR 0.89, 95% CI 0.25-3 , 2) or greater than 500 ms (OR 0.11, 95% CI 0.007 -1.7), according to Elizabeth Park, MD, of Columbia University in New York City.
“Hydroxychloroquine is a key therapy for SLE and is used as monotherapy and combined with other disease-modifying antirheumatic drugs in RA,” he noted at a news conference.
“With long-term use of hydroxychloroquine, however, metabolites of the drug can build up in tissues such as the skin, eyes and heart, with the heart being the most potentially life-threatening concern,” he said.
“Additionally, its use in the treatment of COVID-19 has raised concerns about the possibility of QTc interval prolongation and the development of arrhythmias. In one study, up to 19% of patients demonstrated QT intervals greater than 500 milliseconds and a ratio torsades de pointes, which is a potentially fatal arrhythmia, “he said.
Therefore, to examine the possibility that HCQ, typically considered a very safe treatment in SLE and RA, could have a negative cardiovascular impact on these patients, Park and his colleagues looked at the ECG results of two potential cohorts of RA patients (n = 307) and a retrospective cohort of SLE patients (n = 374), all without clinical cardiovascular disease.
Among the entire study population of 681 patients, 54% were in HCQ and 44% had a QTc greater than 440 ms (mean 437 ms).
The SLE and RA cohorts were also considered separately. For the AR cohort, HCQ use was not associated with a prolonged QTc greater than 440 ms (OR 1.1, 95% CI 0.54-2.2) or greater than 500 ms (OR 0.80, 95% CI 0.23-2.8).
In the SLE cohort, the drug was not associated with a prolonged QTc greater than 440 ms (OR 2, 95% CI 0.46-8.8). While nine of the 11 patients with QTc greater than 500 ms were taking HCQ, these numbers were too small to detect significant differences.
“Importantly, QTc greater than 500 ms was not associated with arrhythmias or death,” he said.
Overall, the use of HCQ in combination with other drugs that can prolong QTc has been associated with QTc lengths similar to those of HCQ alone (434 ms, 95% CI 430-439, vs 433 ms, 95% CI 429 -437).
An exception was that, among SLE patients who were on HCQ plus an antipsychotic, the QTc interval was numerically longer than those with HCQ alone (441 ms, 95% CI 428-454, vs 432 ms, 95% CI 428-436).
“Our findings reinforce the fact that hydroxychloroquine remains a safe and effective long-term disease-modifying drug for our patients with rheumatic diseases,” Park said.
It’s also important to recognize that HCQ-treated COVID-19 patients may have been critically ill and that COVID-19 itself can affect the heart, he said. Additionally, many of the patients were also given azithromycin, which is another drug that prolongs the QTc interval, he added.
Disclosures
Parks reported no financial conflicts. Its co-authors reported financial relationships with AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, and Pfizer.
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