While Mortality Wanes for RA, Patients Still at Higher Risk of All-Cause Mortality

While rheumatoid arthritis (RA)-related deaths have dropped over the last 2 decades, patients with the condition still face a higher risk of mortality compared with patients without RA, say study findings.

The observational study, which collected data from patients at the Veteran’s Health Administration (VHA) between 2000 and 2007, found that 25% of deaths were premature and that mortality associated with RA resulted from cardiovascular, cancer, and respiratory causes. Drawing on their findings, the researchers of the study are calling for ongoing efforts dedicated to improving the lifespan of these patients.

“Our results suggest that these efforts should be directed at cardiopulmonary diseases that included CVD, respiratory disease, and lung cancer, which together explained nearly 70% of the >2,500 excess deaths that occurred among patients with RA,” noted the researchers. “This is the first study, to our knowledge, to examine risk and temporal trends in cause-specific mortality in RA using national-level data in the VHA, the largest integrated healthcare system in the U.S.”

The data pool included nearly 30,000 patients with RA, more than 9000 of which died throughout the study period. Though the increased risk of all-cause mortality related to RA dropped from 31% (aHR 1.31, 1.26-1.36) between 2000-2005 to 10% (aHR 1.10, 1.05-1.15) between 2012-2017, they remained at a higher risk of mortality compared with the 245,000 controls.

Compared with controls, patients with RA faced a 19% increased risk of cardiovascular (aHR 1.19, 1.14-1.23) and cancer (aHR 1.19, 1.14-1.24) mortality, a 46% (aHR 1.46, 1.38- 1.55) increased risk of respiratory mortality, and 59% (aHR 1.59, 1.41-1.80) increased risk of infection-related mortality.

Across all causes, cause of death from interstitial lung disease (ILD) was most strongly related to RA (aHR 3.39, 2.88-3.99). The group also found a high risk of chronic obstructive pulmonary disease (COPD), which was the most frequent case of respiratory-related death. among the patients with RA (aHR 1.24, 95% CI 1.15-1.33).

“Our findings reflect the increased incidence of both ILD and COPD in RA, even after accounting for cigarette smoking history, and the impact of these conditions on survival. Despite recognition of these epidemiologic findings, there are no standard approaches for the identification or management of RA-associated lung diseases,” flagged the researchers. “This study emphasizes the need for developing and evaluating such approaches to eliminate the persistent mortality burden posed by these conditions in patients with RA.”

Among cardiovascular disease-related mortality, the researchers found several causes overrepresented in patients with RA, primarily CAD (aHR 1.17, 95% CI 1.10-1.23) and heart failure (aHR 1.28, 95% CI 1.16-1.42). Less frequent causes included valvular heart disease (aHR 1.76, 95% CI 1.36-2.26) and venous thromboembolism (VTE) (aHR 1.57, 95% CI 1.10-2.51).

Both RA itself and the use of DMARDS, particularly Janus kinase (JAK) inhibitors, have been subjects of interest for VTE risk, though due to the study period and infrequent use of JAK inhibitors within the VHA, the researchers attributed the VTE mortality seen in their study to RA rather than DMARDS.

The group suggested that future studies look at how temporal trends in RA management, including with glucocorticoids, may affect differences in mortality risk.

Reference

Johnson TM, Yang Y, Roul P, et al. A narrowing mortality gap: temporal trends of cause-specific mortality in a national, matched cohort study in U.S. veterans with rheumatoid arthritis. Arthritis Care Res. Published online November 4, 2022. doi:10.1002/acr.25053