Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen‐Year Follow‐up

• Published in: Arthritis care & research (2010) 2023-07, Vol.75 (7), p.1571-1579
• Main Authors: Quiñones, Mercedes E., Joseph, Joyce K., Dowell, Sharon, Moore, Hans J., Karasik, Pamela E., Fonarow, Gregg C., Fletcher, Ross D., Cheng, Yan, Zeng‐Treitler, Qing, Arundel, Cherinne, Liappis, Angelike P., Sheriff, Helen M., Zhang, Sijian, Taub, Daniel D., Heimall, Michael S., Faselis, Charles, Kerr, Gail S., Ahmed, Ali
• Format: Article
• Language: English
• Subjects: Aged; Antirheumatic Agents - adverse effects; Arrhythmia; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - epidemiology; Cohort analysis; Cohort Studies; Female; Follow-Up Studies; Humans; Hydroxychloroquine; Hydroxychloroquine - adverse effects; Long QT syndrome; Long QT Syndrome - chemically induced; Long QT Syndrome - diagnosis; Long QT Syndrome - epidemiology; Male; Methotrexate - therapeutic use; Middle Aged; Retrospective Studies; Rheumatoid arthritis; Veterans
• ISSN: 2151-464X; 2151-4658
• DOI: 10.1002/acr.25005

Objective Recent evidence suggests that hydroxychloroquine use is not associated with higher 1‐year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long‐term risk, the examination of which was the objective of this study. Methods We conducted a propensity score–matched active‐comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease‐modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19‐year follow‐up through December 31, 2019. Results Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5‐year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217–1,740) and a 181% greater relative risk (95% CI 11%–613%; P = 0.030). Although overall 10‐year risk remained significant (hazard ratio 2.17; 95% CI 1.13–4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6–10) and 1 over the next 9 years (years 11–19). There was no association with arrhythmia‐related hospitalization or all‐cause mortality. Conclusions Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5‐year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow‐up. These findings provide evidence for long‐term safety of hydroxychloroquine in patients with RA.