Key result
Hydroxychloroquine use in rheumatoid arthritis was associated with a higher 5-year risk of long QT syndrome compared to other DMARDs (0.38% vs 0.14%; P=0.030), though absolute risk was very low.
Why the study?
Hydroxychloroquine is not linked to higher 1-year long QT syndrome risk in rheumatoid arthritis, but its long-term risk remains poorly understood.
Does hydroxychloroquine increase the risk of long QT syndrome in veterans with newly diagnosed rheumatoid arthritis?
Cohort (n=8,852)
Does hydroxychloroquine increase the risk of long QT syndrome in veterans with newly diagnosed rheumatoid arthritis?
Effect estimate: 181% greater relative risk (95% CI 11%-613%)
Absolute Event Rate: 0.38% vs 0.14%
p-value: p=0.030
Hydroxychloroquine use in rheumatoid arthritis is associated with a very low absolute risk of long QT syndrome over 19 years, providing evidence for its long-term safety.
Very low absolute risk supports ongoing hydroxychloroquine use in RA; leaves open causality and generalizability.
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.
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Quinones et al. (2022) conducted a cohort in rheumatoid arthritis (n=8,852). hydroxychloroquine vs. another nonbiologic disease-modifying antirheumatic drug (DMARD) was evaluated on long QT syndrome (LQTS) during 19-year follow-up (181% greater relative risk, 95% CI 11%-613%, p=0.030). Hydroxychloroquine use in rheumatoid arthritis was associated with a higher 5-year risk of long QT syndrome compared to other DMARDs (0.38% vs 0.14%; P=0.030), though absolute risk was very low.
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