Differences in Cause-Specific Mortality in Patients With Rheumatoid Arthritis by Sex and Seropositivity

Our aims were to investigate the trends in observed vs expected all-cause mortality and the effects of serostatus and sex on all-cause and cause-specific mortality in individuals with rheumatoid arthritis (RA) in a large community-based longitudinal cohort study.

This retrospective cohort study evaluated all-cause and cause-specific mortality in RA using a community population-based inception cohort of adult residents of Olmsted County, Minnesota, with incident RA from 1980 to 2019 meeting American College of Rheumatology 1987 criteria, and non-RA residents matched 3:1 to patients with RA by age and sex. Underlying cause of death was obtained from death certificates. Competing risks/cumulative incidence methods were used to compare cause-specific mortality incidence between individuals with and without RA. Cox models estimated the effect of RA on risk of cause-specific mortality, adjusting for sex, age, and calendar year of index. Interactions for RA with sex, age, seropositivity, and calendar year were examined.

The study included 1337 patients with RA and 4011 non-RA comparators. All-cause mortality was significantly increased in both female and male individuals with RA, specifically in seropositive RA, and declined after the 1980s. The increased risk of death due to respiratory causes in patients with RA was significantly different depending on seropositive vs seronegative status (adjusted hazard ratio 2.26 [95% CI 1.56-3.26] vs 0.52 [95% CI 0.24-1.13], interaction P < 0.001). There were no significant differences in cause-specific mortality based on sex.

Seropositivity in persons with RA associates with a significantly increased risk of death, particularly due to respiratory causes, whereas no increased risk was found in seronegative patients.