Risk of Arrhythmia Among New Users of Hydroxychloroquine in Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population-Based Study.

OBJECTIVES: We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE). METHODS: All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow-up. We used cause-specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes. RESULTS: We identified 11,518 propensity score-matched patients with RA or SLE in each group. Over the mean follow-up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause-specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89-1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83-1.04), 0.98 (95% CI 0.87-1.11), and 0.95 (95% CI 0.84-1.07), respectively. CONCLUSION: Risk of any type of arrhythmia was not increased among new users of HCQ.

Impact of Antimalarial Adherence on Mortality Among Patients With Newly Diagnosed Systemic Lupus Erythematosus: A Population-Based Cohort Study.

OBJECTIVE: To assess the association of antimalarial (AM) adherence with premature mortality among incident systemic lupus erythematosus (SLE) patients. METHODS: All patients with incident SLE and incident AM use in British Columbia, Canada, between January 1997 and March 2015 were identified using the provincial administrative databases. Follow-up started on the first day of having both SLE and AM. The outcome was all-cause mortality. An adherence measure, proportion of days covered (PDC), was calculated and categorized as adherent (PDC ≥ 0.90), nonadherent (0 < PDC < 0.90), and discontinuer (PDC = 0) during 30-day windows. We first used Cox models for time-to-death, adjusting for baseline and time-varying confounders on medication usages, health care utilization, and comorbidities. We then used marginal structural Cox models via inverse probability weighting designed for causal inference with time-varying confounders to assess the effect of AM adherence on premature mortality. RESULTS: We identified 3,062 individuals with incident SLE and incident AM use (mean age 46.9 years). Over the mean follow-up period of 6.4 years, 242 (7.9%) of those patients died. Adjusted hazard ratios (HRadj ) from the Cox model for AM adherent and nonadherent SLE patients were 0.20 (95% confidence interval [95% CI] 0.13-0.29) and 0.62 (95% CI 0.42-0.91), respectively, compared to discontinuers. The corresponding HRadj from the marginal structural Cox model were 0.17 (95% CI 0.12-0.25) and 0.58 (95% CI 0.40-0.85), respectively. A significant trend in the HRadj of mortality risk over the adherence levels was found (P < 0.001). CONCLUSION: Patients with SLE adhering to AM therapy had a 71% and 83% lower risk of death than patients who do not adhere or who discontinued AMs, respectively.