Examining Mortality Risk Factors in Ankylosing Spondylitis

Ankylosing spondylitis (AS) patients face a greater risk of mortality, but treatment with tumor necrosis factor inhibitors erases it.

Patients with ankylosing spondylitis (AS) had a greater risk of mortality than the general population, but treatment with tumor necrosis factor inhibitors (TNFi) erased the additional hazard, according to a new study.

The study, published in Arthritis Care and Research, noted certain risk factors for higher levels of mortality, including male sex, some comorbidities, and higher C-reactive protein levels.

After adjusting for age, gender, and other factors, researchers found the adjusted hazard ratio (HR) for mortality was 1.19 compared to the control group (95% CI, 1.10-1.30), P < .001). After adjusting for baseline comorbidities—such as chronic pulmonary disease, connective-tissue diseases, ischemic heart disease, peptic ulcer disease, and malignancies—the HR was 1.14 (95% CI, 1.05-1.24).

However, for patients treated with TNFi (HR = 0.67; 95% CI, 0.38-1.18) or a combination of TNFi and disease-modifying antirheumatic drugs (DMARD), there was no increased mortality rate (HR = 0.93; 95% CI, 0.69-1.25).

AS is a chronic inflammatory disease affecting the spine and large joints, with other manifestations including psoriasis, inflammatory bowel disease, eye inflammation, and abnormalities in conduction of signals within the heart muscle. Prevalence is estimated at 9 to 30 per 10,000 persons. In addition to TNFi and DMARDs such as methotrexate or sulfasalalzine, AS is commonly treated with nonsteroidal anti-inflammatory agents and the interleukin 17 inhibitor secukinumab (Cosentyx).

This study was launched largely because of a scarcity of research since the early days of treating AS with spinal radiation, the authors said. Those that were conducted showed excess mortality compared with the general population but had small sample sizes and other limitations.

The current study comprised 5930 patients with and an additional 29,018 from a control group in Israel; they were followed for a median period of 7.5 years. The cohort consisted of patients diagnosed with AS from 2002 to 2018.

Among patients with AS, increased age (odds ratio [OR] = 3.02; 95% CI, 2.79-3.27; P < .001) and male gender (OR = 1.56; 95% CI, 1.27-1.90; P < .001) were significantly associated with mortality. Ethnicity and socioeconomic status were not.

Beneficial effects of TNFi on mortality overall were previously reported for chronic inflammatory rheumatic diseases such as rheumatic arthritis and psoriatic arthritis. In the study, for patients treated with TNFi and in combination with DMARDs, there was excess mortality if the time for initiating treatment was longer.

In the AS group, there were 667 deaths; in the control group, there were 2919. The mean age at death was 76.9 years in the AS group and 77.1 in the control group. Nearly 56% of patients with AS were treated solely with NSAIDs, while 30.2% were treated with TNFi, and 29% with DMARDs.

TNFi agents were introduced 2 decades ago and are not only effective against AS but also protective against atherosclerosis, the study said.


Ben-Shabat N, Shabat A, Watad A, et al. Mortality in ankylosing spondylitis according to treatment: A nationwide retrospective cohort study of 5900 patients from Israel. Arthritis Care Res. Published online May 10, 2021. doi:10.1002/acr.24616.

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