Ankylosing Spondylitis Tied to Increased All-Cause Mortality

Janis C. Kelly

September 23, 2015

Ankylosing spondylitis (AS) was associated with increased risk for death, particularly in poor patients, in patients with multiple health problems, and in patients who had had hip replacements, according to a study published online September 2 in the Annals of the Rheumatic Diseases.

The study, by Sofia Exarchou, MD, from the Rheumatology Section, Department of Clinical Sciences, Lund University, Malmö, Sweden, and colleagues, included 8600 patients with AS and 40,460 matched comparator subjects. The authors note that it is the first study to document increased all-cause mortality in a nationwide AS cohort.

Dr Exarchou said the researchers were surprised to find that disease-related clinical manifestations such as psoriasis, inflammatory bowel disease, uveitis, peripheral arthritis, and aortic insufficiency were not associated with increased risk for death in patients with AS. However, the authors suggest that hip replacement might be a marker for disease burden.

The study cohort included patients with AS diagnosed at rheumatology or internal medicine outpatient clinics. Five comparator subjects were matched to each patient with AS by age, sex, and county of residence. Follow-up was from January 1, 2006, or date of registered diagnosis until death, emigration, or December 31, 2012, whichever occurred first.

The age-adjusted and sex-adjusted hazard ratio (HR) for risk of death was 1.60 for the AS cohort compared with the control cohort (496/8600 vs 1533/40,460; 95% confidence interval [CI], 1.44 - 1.77). The increased risk for death was apparent both in men (age-adjusted HR, 1.53; 95% CI, 1.36 - 1.72) and women (age-adjusted HR, 1.83; 95% CI, 1.50 - 2.22) with AS. Because male sex and higher age were independent predictors of AS mortality, all other possible predictors were adjusted for age and sex.

Estimated 6-year survival was 94.5% (95% CI, 93.9% - 95.0%) for the patients with AS and 96.9% (95% CI, 96.7% - 97.1%) for the control subjects. The authors note that the relative mortality risk in AS was similar to that reported previously for patients with rheumatoid arthritis (RA).

Cardiovascular disease was the major cause of death in the AS cohort and was more frequent in the patients with AS than in control subjects (34.7% vs 30.6%). Other factors associated with higher mortality risk included lower level of education, chronic pulmonary disease, cancer, infections, and history of hip replacement.

Nigil Haroon, MD, assistant professor of rheumatology and medicine, University of Toronto, Ontario, Canada, who was not involved in the study, told Medscape Medical News, "Exarchou and colleagues have done commendable work to assess all-cause mortality in AS. The findings confirm our recent report of increased cardiovascular and cerebrovascular mortality in AS. Hip involvement is considered a marker of severity, and the results would suggest that severity of AS could be linked to mortality. There has been emphasis on a window of opportunity in the treatment of AS in recent times, and this data would support early and [appropriate] treatment for AS."

Dr Exarchou said the researchers had expected to find increased mortality associated with AS but were surprised at the magnitude of the increase. "Clinical measures indicating more severe clinical status predict premature death in RA, suggesting that inflammation and chronic disease play an important role on mortality in RA. AS has a different age- and sex-distribution, pathology, and phenotype compared to RA. However, although the burden of inflammation may not be the same in both diseases, AS is still a disease with often pronounced systemic inflammation. Our finding that AS is associated with increased mortality was thus not surprising, although the magnitude of the effect was slightly larger than we anticipated," she told Medscape Medical News.

The researchers were not able to assess the effect of drug therapy such as nonsteroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factors inhibitors on AS mortality. Dr Exarchou said, "The role of pharmacological therapies on mortality in AS is an important question, since they simultaneously have beneficial anti-inflammatory effects and adverse events." She said that limited evidence has suggested an association of infrequent use of NSAIDs with increased mortality in AS, but that this is difficult to interpret because it might reflect prescribing of NSAIDs to patients with less severe disease, rather than a true protective effect.

Dr Exarchou said, "Future studies addressing this important question [of the impact of drug therapy] are warranted. However, it is still very possible that effective treatment with, for example, [tumor necrosis factors inhibitors] could have a beneficial effect also in mortality in AS, since such an effect has been shown in rheumatoid arthritis."

Dr Exarchou added, "Although the exact role of inflammation and treatment on mortality risk in AS has not been addressed by our study, it is still likely to be related to mortality. Thus, the aim of the physician should be to treat the disease to target (remission) in order to minimize the inflammation burden, taking always into consideration the contraindications and the side-effects of existing treatments."

The researchers suspect socioeconomic status may be a marker of the patient's ability to manage other risk factors for mortality, such as poor diet, cigarette smoking, lack of exercise, poor coping and problem-solving skills, or inefficiency in using medical services. Dr Exarchou advised clinicians to be alert for such patients with AS and try to modify these risk factors.

The study was funded by the Oak foundation, the Swedish Rheumatism Association, and the Lund University. The authors and Dr Haroon have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online September 2, 2015. Abstract

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