TNF inhibitor tapering may raise risk of disease flare in AS: Review

Tapering off a TNF inhibitor — part of a class of medications that block pro-inflammatory molecules — may raise the risk of disease flare in people with spondyloarthritis, including among those with ankylosing spondylitis (AS), compared with staying on a standard dose, according to a review study.

Further research is needed to find safe tapering strategies for these anti-TNF therapies, and to identify patients who can taper off their medications without risking symptom worsening, even if disease activity is low, the researchers noted.

“The strategy of [TNF inhibitor] tapering was associated with a significantly increased risk of disease flare compared to maintaining [spondyloarthritis] patients at the standard TNF dose,” the team wrote.

The study, “Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review,” was published in the journal International Immunopharmacology by a team of researchers in South Korea.

No detailed strategy is in place for dose tapering among patients

Spondyloarthritis is a group of diseases characterized by inflammation in the spine and the joints. Ankylosing spondylitis is a form of spondyloarthritis that mainly damages the spine.

Anti-TNF therapies, also known as TNF inhibitors, are a class of medications approved for ankylosing spondylitis and other forms of spondyloarthritis that work by blocking the activity of the pro-inflammatory molecule tumor necrosis factor, or TNF.

While this type of therapy has been shown to help ease pain and reduce disease activity, lessening symptoms such as fatigue, it may cause side effects such as an increased risk for infections and skin disorders. TNF inhibitors also are costly, which adds to the burden of both patients and the healthcare system.

Current clinical guidelines suggest tapering off anti-TNF therapies — gradually reducing their doses or increasing their dosing intervals — only in spondyloarthritis patients who have achieved sustained disease remission.

But “a detailed strategy for dose tapering and the critical points to be considered before tapering [anti-TNF therapies] have not been established,” the researchers wrote.

To compare the risk of disease flare between patients who tapered off versus those who continued taking their standard doses of a TNF inhibitor, the researchers systematically reviewed published studies through August 2023 reporting on such comparisons.

A total of nine appropriately-controlled clinical trials and three observational studies were included in their meta-analysis — one that combines data from multiple studies.

The 12 studies involved 2,237 spondyloarthritis patients with sustained remission or low disease activity. Among them, 1,301 continued standard dose treatment while 936 underwent tapering. Nine studies involved people with ankylosing spondylitis.

Most of the studies evaluated the occurrence of disease relapses, or flares, over a period of one year or longer; two monitored flares for six months. Determining the occurrence of flares was based on standardized measures of disease activity.

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60% greater odds of relapse found for those tapering off a TNF inhibitor

Disease flares occurred in 216 patients (16.6%) who continued taking their standard doses, and among 217 patients (23.2%) who underwent dose tapering. Pooled data showed that this translated into a 60% increase in the odds of experiencing a relapse if patients tapered off their TNF inhibitor.

These findings highlight that, among spondyloarthritis patients with disease remission or low disease activity, tapering off anti-TNF therapies may help avoid side effects and reduce costs. However, it also may increase the risk of disease flares.

“The appropriateness of [TNF inhibitor] tapering should be carefully assessed, and patients should be made aware of the risk of disease flare even if disease activity is low or in remission,” the team wrote.

Among the limitations of their meta-analysis, the researchers noted the small number of included studies and the variability between the works in terms of disease flare definitions. In addition, the fact that these studies did not provide detailed outcome data for each type of spondyloarthritis means that “it is possible that outcome may differ by subtype,” they wrote.

The appropriateness of [TNF inhibitor] tapering should be carefully assessed, and patients should be made aware of the risk of disease flare even if disease activity is low or in remission.

“Further studies are needed to determine which patients can safely undergo tapering of [TNF inhibitors] and to develop safe tapering strategies,” the researchers wrote.

“Several multicenter prospective clinical trials aiming to evaluate clinical efficacy, adverse events, and predictors of [TNF inhibitor] tapering in [spondyloarthritis] patients are ongoing, and it is expected that the results will be published in the near future,” the team concluded.