Early Anti-TNF Therapy May Raise Risk of Cardiovascular Disease in AS

However, potentially influencing factors were not accounted for in the analyses

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by Andrea Lobo |

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Early initiation of anti-tumor necrosis factor (TNF) medications may be associated with an increased risk of cardiovascular events in people with ankylosing spondylitis (AS), a study suggests.

“We designed the study with the overall hypothesis that the use of TNF inhibitors, which reduce inflammation and thus cardiovascular risk, would be associated with lower risk for our cardiovascular outcomes” in AS patients,” Jean Liew, MD, the study’s first author, said in a press release from the American College of Rheumatology (ACR).

“That we saw the opposite association, that early use of TNF inhibitors was associated with a higher risk of incident cardiovascular outcomes, was a bit surprising,” added Liew, who’s also an assistant professor at Boston University.

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Potentially influencing factors were not included in analysis

Still, further research adjusting for potentially influencing factors that could not be included in the current analysis is needed to confirm whether these findings represent ‘the real truth,’ Liew emphasized.

The results were presented in a poster, titled “The Association of Early TNF Inhibitor Use with Incident Cardiovascular Events in Ankylosing Spondylitis,” at the ACR Convergence 2022, ACR’s annual meeting, being held Nov. 10–14, in Philadelphia.

People with ankylosing spondylitis, a type of arthritis characterized mainly by the inflammation in the joints of the spine, have an increased risk of cardiovascular disease.

While anti-TNF therapies, which work by blocking the activity of the pro-inflammatory molecule TNF, are effective in treating AS symptoms, their effects on cardiovascular disease are unknown.

To address this, Liew and colleagues in the U.S. analyzed data from 17,666 AS patients within the Veteran Affairs Corporate Data Warehouse, one of the largest healthcare information systems in the U.S., from 2002 to 2019.

The research was supported by funding from the Rheumatology Research Foundation and the Spondyloarthritis Research and Treatment Network.

The whole healthcare team needs to be cognizant of screening for and treating traditional cardiovascular risk factors

Patients who started anti-TNF therapy early tended to be younger

The presence of AS was defined as one or more inpatient or two or more outpatient international code disease (ICD) for AS, separated by at least six weeks. ICD is the official code for each disease, allowing clinicians from around the world to compare and share data consistently.

The mean age of the patients was 59.5 years, and the majority were men (91.2%) and white (79.8%). They were followed up for a mean of six years.

A total of 2,321 patients initiated anti-TNF therapy early in their disease course, defined as occurring in the 12 months following the first AS ICD.

These patients were younger, and had a lower prevalence of high blood pressure and diabetes — two risk factors of cardiovascular disease — relative to those who did not initiate treatment early.

During follow-up, cardiovascular disease was reported in 351 (15.1%) of patients starting anti-TNF medication early, compared with 3,020 (19.7%) of those who did not.

The team then conducted propensity score analyses, which allow group comparisons between patients with similar demographic and clinical characteristics. These were also performed in two calendar periods (2002–2010 and 2011–2019) to account for secular trends in AS and cardiovascular management.

Results showed that early initiation of anti-TNF therapy was significantly associated with a higher risk of cardiovascular disease (by 17%), stroke (by 24%), and major adverse cardiovascular events (by 22%). These significant associations were observed in the 2011–2019 period, but not in the preceding period.

However, potentially influencing factors were not accounted for in the analyses, which might have biased the results, Liew noted.

Researchers did not have information about disease activity in patients, which is “an important [potentially influencing factor] that is associated with early TNF inhibitor initiation and cardiovascular outcomes,” Liew said.

If such information was included in the analysis, “perhaps we would not have seen a statistically significant association between early TNF inhibitor initiation and cardiovascular disease,” Liew added.

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In addition, the team cannot exclude the possibility that residual confounding by indication occurred. This means that the reason why patients are prescribed one medication over another might be related to their chances of having the analyzed outcome. However, the reason why a medication is prescribed is frequently missing.

Future studies, accounting for these important influencing factors, are needed to confirm these findings.

Still, doctors can address the increased risk of cardiovascular disease in AS patients, Liew noted.

“The whole healthcare team needs to be cognizant of screening for and treating traditional cardiovascular risk factors like hypertension and [high blood levels of fatty molecules],” she said.

“This burden cannot be placed on either the rheumatologist alone, who doesn’t typically manage these conditions, or the primary care provider alone who is likely unaware of the heightened cardiovascular risk,” she added.