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.