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

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.

How to use biologic agents in patients with rheumatoid arthritis who have comorbid disease.

Although biologic disease modifying anti-rheumatic drugs (bDMARDs) have improved the quality of life of patients with rheumatoid arthritis, side effects remain a problem, especially for patients with pre-existing comorbidities. Randomized controlled trials of such drugs in rheumatoid arthritis typically exclude patients with comorbidities and are of short duration, so they do not provide data on adverse events in these people. Other data sources such as national bDMARD registries are limited by the preselection of patients for both conventional synthetic chemical compound disease modifying anti-rheumatic drugs (csDMARDs) and bDMARDs, and although these databases document comorbidity, they rarely report its severity. This too limits definitive statements on the progression or resolution of pre-existing disease. Although bDMARDs may not be contraindicated in patients with rheumatoid arthritis and certain comorbid diseases, additional assessments or precautions are recommended. This review summarizes current data on the use of bDMARDs in people with rheumatoid arthritis and common comorbid diseases. It provides an evidence base for doctors and their patients when discussing and selecting the appropriate bDMARDs.