Study Suggests TNF Inhibitor Use Is Cardioprotective in Radiographic Axial Spondyloarthritis

Tumor necrosis factor inhibitor (TNFi) use was associated with a lower risk of cardiovascular (CV) outcomes in patients with radiographic axial spondyloarthritis (r-axSpA) in a recent study, adding to data surrounding the management of this high-risk population. The findings were published in Seminars in Arthritis and Rheumatism.¹

Axial spondyloarthritis (axSpA) is a type of arthritis primarily impacting the spine and sacroiliac joint, but it is systemic and can also impact other areas of the body.² Radiographic axSpA is characterized by damage that can be seen on x-rays. Patients with r-axSpA have a higher risk of cardiovascular disease (CVD) and CVD-related mortality vs those without r-axSpA, which could potentially be explained in part by a higher prevalence of risk factors like hypertension or systemic inflammation compared with the general population.¹

Although nonsteroidal anti-inflammatory drugs are the typical first-line pharmacologic therapy in axSpA, their potential to increase CV risk can limit their use in this population.

Axial spondyloarthritis (axSpA) is a type of arthritis primarily impacting the spine and sacroiliac joint. | Image credit: Mantinov - stock.adobe.com

“Emerging evidence in other rheumatologic diseases suggests that TNFis, which are currently second-line pharmacotherapy, may be cardioprotective through control of the underlying inflammatory disease,” the authors explained. “However their impact on both CV risk factors and individual CV events such as myocardial infarction (MI) and venous thromboembolism (VTE) remains unclear.”

The relationship between r-axSpA and CV risk is not as well defined as in other rheumatic conditions, and there are no data-driven guidelines for managing excess CVD risk or burden in patients with r-axSpA.

“Understanding how axSpA-directed therapies impact CV risk factors and outcomes is essential for developing strategies to limit excess CV risk in patients with r-axSpA,” the authors wrote. The study aimed to determine the association between TNFi use and cardiovascular outcomes in r-axSpA in a large cohort of patients with data in the Veterans Affairs Clinical Data Warehouse with CMS linkage.

When the researchers applied a recently published multimodal automated phenotyping (MAP) method utilizing a main International Classification of Diseases (ICD) code and natural language processing of electronic health record data, they identified a total of 26,928 patients with a new diagnosis of r-axSpA, with 3663 using TNFis and 23,295 not using TNFis at baseline. The mean age was 63.4 years, 94% of patients were male, and 82% were White. Using ICD codes exclusively, they found 30,626 individuals diagnosed with r-axSpA, including 3791 who were TNFi users and 26,835 who were not using TNFis at baseline. The mean age was 65.0 years, 94% of patients were male, and 83% were White. A total of 16,920 fit both the ICD code and MAP definitions of r-axSpA, while 13,706 only fit the ICD code definition, and 10,008 only fulfilled only the MAP definition.

At a mean (SD) follow-up of 3.3 (4.2) years, 674 TNFi users (18.6%) in the MAP-defined cohort had incident CVD compared with 11,838 nonusers (50.8%). MI, stroke, and VTE were also more common in nonusers compared with TNFi users. There were 22 occurrences of all-cause mortality among TNFi users (0.6%) and 9249 among nonusers (39.7%) during follow-up.

TNFi use vs nonuse was also associated with lower risk of incident CVD in adjusted analyses in both the MAP (HR, 0.34; 95% CI, 0.29-0.40) and ICD (HR, 0.34; 95% CI, 0.29-0.39) cohorts from 2002 to 2010 and from 2011 to 2019.

Study limitations included the potential misclassification of r-axSpA based on the use of ICD codes, although the cohort developed with the MAP algorithm aimed to mitigate this limitation. Still, algorithms rely on electronic health records, the authors noted. Misclassification of exposure to TNFis or of MI and VTE outcomes are also possibilities. The findings may also not be generalizable outside of the veteran population.

“As observational data accumulate, the totality of evidence may support future changes in clinical practice to prevent or manage CVD risk in those with r-axSpA,” the authors concluded. “When engaging in shared decision making with patients, clinicians should continue to address the balance of risks and benefits of the available treatments, especially regarding the association of CVD with active systemic inflammation.“

References

1. Liew JW, Treu T, Park Y, et al. The association of TNF inhibitor use with incident cardiovascular events in radiographic axial spondyloarthritis. Semin Arthritis Rheum. Published online June 2, 2024. doi:10.1016/j.semarthrit.2024.152482

2. Ankylosing spondylitis & nonradiographic axial spondyloarthritis. Arthritis Foundation. Accessed June 7, 2024. https://www.arthritis.org/diseases/ankylosing-spondylitis