To assess the association of antimalarials (AM) adherence with premature mortality among incident systemic lupus erythematosus (SLE) patients.
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), non-adherent (0<PDC<0.90), and discontinuer (PDC=0) during 30-day windows. We first used Cox's models for time-to-death, adjusting for baseline and time-varying confounders on medication usages, healthcare 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.
We identified 3,062 individuals with incident SLE and incident AM use (mean age 46.9 years). Over the mean follow-up of 6.4 years, 242 (7.9%) of them died. Adjusted hazard ratios (aHRs) from Cox's model for AM adherent and non-adherent SLE patients were 0.20 (95% CI:0.13-0.29) and 0.62 (95% CI:0.42-0.91), respectively, compared to discontinuers. The corresponding aHRs 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 aHRs of mortality risk over the adherence levels was found (p-value:<0.001).
SLE patients adhering to AM therapy had a 71% and 83% lower risk of death than patients who do not adhere or who discontinue AM, respectively.