A Narrowing Mortality Gap: Temporal Trends of Cause‐Specific Mortality in a National Matched Cohort Study in US Veterans With Rheumatoid Arthritis

Abstract

Objective To examine temporal trends in all‐cause and cause‐specific mortality in patients with rheumatoid arthritis (RA) in the Veterans Health Administration (VHA). Methods We conducted a matched cohort study in the VHA from January 1, 2000 to December 31, 2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non‐RA patients, then followed until death or end of study period. Cause of death was obtained from the National Death Index. Multivariable Cox regression models stratified by RA diagnosis years were used to examine trends in RA‐related risk of all‐cause and cause‐specific mortality. Results Among 29,779 incident RA patients (matched to 245,226 non‐RA patients), 9,565 deaths occurred. RA patients were at increased risk of all‐cause (adjusted hazard ratio [HRadj] 1.23 [95% confidence interval (95% CI) 1.20–1.26]), cardiovascular (HRadj 1.19 [95% CI 1.14–1.23]), cancer (HRadj 1.19 [95% CI 1.14–1.24]), respiratory (HRadj 1.46 [95% CI 1.38–1.55]), and infection‐related mortality (HRadj 1.59 [95% CI 1.41–1.80]). Interstitial lung disease was the cause of death most strongly associated with RA (HRadj 3.39 [95% CI 2.88–3.99]). Nearly 70% of excess deaths in RA were attributable to cardiopulmonary disease. All‐cause mortality risk related to RA was lower among those diagnosed during 2012–2017 (HRadj 1.10 [95% CI 1.05–1.15]) compared to 2000–2005 (HRadj 1.31 [95% CI 1.26–1.36]), but still higher than for non‐RA controls (P < 0.001). Cause‐specific mortality trends were similar. Conclusion Excess RA‐related mortality was driven by cardiovascular, cancer, respiratory, and infectious causes, particularly cardiopulmonary diseases. Although our findings support that RA‐related mortality risk is decreasing over time, a mortality gap remains for all‐cause and cause‐specific mortality in RA.

Aortic Stenosis Risk in Rheumatoid Arthritis

“…18,29 We found that patients with RA had an increased risk (AHR, 1.26; 95% CI, 1.04-1.54) of AS-related death, a mortality risk similar to that of ischemic heart disease in previous RA cohorts. 8,27 These data support a more severe AS disease course in contrast to a smaller study that reported similar AS progression rates in patients with RA and control patients, although that study had a shorter follow-up time and did not examine clinical AS outcomes. 30 The findings from the present study emphasize that valvular heart disease may be an underrecognized contributor to the persistent CVD-related mortality gap in RA, 8 particularly given the lack of improvement in ASspecific risk over time.…”

“…We found that patients with RA had an increased risk (AHR, 1.26; 95% CI, 1.04-1.54) of AS-related death, a mortality risk similar to that of ischemic heart disease in previous RA cohorts . These data support a more severe AS disease course in contrast to a smaller study that reported similar AS progression rates in patients with RA and control patients, although that study had a shorter follow-up time and did not examine clinical AS outcomes .…”

“…In a recent analysis of temporal trends in RA-related cause-specific mortality risk from our research group, contemporary RA cohorts had a persistently increased risk of CVD-related mortality . This included a 75% increased risk of valvular heart disease–related death, the most overrepresented cause of CVD death in RA.…”

“…[5][6][7] In a recent analysis of temporal trends in RA-related causespecific mortality risk from our research group, contemporary RA cohorts had a persistently increased risk of CVD-related mortality. 8 This included a 75% increased risk of valvular heart disease-related death, the most overrepresented cause of CVD death in RA. However, valvular heart disease is rarely described as an extra-articular manifestation of RA, and investigations in RA have largely been limited to small echocardiographic studies describing the prevalence of valvular abnormalities without longitudinal outcomes.…”

Cancer Risk in Patients Treated with the JAK Inhibitor Tofacitinib: Systematic Review and Meta-Analysis

“…Moreover, patients in the ORAL Surveillance study [ 19 ] were all over 50 years and had at least one major cardiovascular risk factor (e.g., smoking) that increases their neoplastic risk. In the rheumatoid arthritis population, malignancy is a leading cause of death [ 40 , 41 ], especially in patients not undergoing immunosuppressive therapy [ 42 ]. Nonetheless, this is also supported by our finding on RA indications, which is the only subgroup confirming the slightly increased risk of cancer in patients undergoing tofacitinib vs. anti-TNF.…”