Increased neuroinflammatory disease risk with TNF inhibitors depends on arthritis type
medwireNews: Research indicates that tumor necrosis factor (TNF) inhibitor treatment is associated with an increased risk for developing neuroinflammatory disease in patients with psoriatic arthritis (PsA) or ankylosing spondyloarthritis (AS), but not in those with rheumatoid arthritis (RA).
“This information will be important for risk communication and evaluation in clinical practice, even though the absolute risk is low,” say Tine Iskov Kopp (Rigshospitalet Glostrup, Denmark) and co-investigators.
They specify: “Since chronic inflammatory diseases have distinct genetic profiles and different distribution of age and sex, these diseases should be separated in the risk analysis.”
The researchers used data pertaining to 175,520 patients who were identified from national registers in Denmark and Sweden between 2000 and 2017, of whom 64,065 had PsA or AS and 111,455 had RA.
During follow-up, which ranged from 2.7 to 7.4 years, a quarter of patients took TNF inhibitors, most commonly infliximab (n=14,163), etanercept (n=13,997), and adalimumab (n=10,260), followed by certolizumab pegol (n=2786) and golimumab (n=2786).
PsA or AS patients taking TNF inhibitors had a greater risk for developing a neuroinflammatory disease than those not exposed to the agents, with a significant 1.50-fold and 3.41-fold increased risk in the Swedish and Danish cohorts, respectively, after adjusting for sex and calendar time.
Specifically, the risk was greatest for a demyelinating disease, at a significant 1.65-fold and 3.00-fold increase in the Swedish and Danish cohorts, respectively, followed by multiple sclerosis, with a 1.65-fold increased risk in the Swedish cohort.
Swedish PsA and AS patients exposed to TNF inhibitors also had an increased risk for developing inflammatory polyneuropathies, but at just 1.13-fold.
By contrast, exposure to TNF inhibitors did not significantly increase the risk for neuroinflammatory diseases in RA patients, with adjusted hazard ratios (HRs) ranging from 0.97 in the Swedish cohort to 1.45 in the Danish cohort, reflecting “an elevated but not significantly increased” risk, according to Kopp and team.
The researchers emphasize that the absolute risk for a neuroinflammatory event in patients taking TNF inhibitors is still low in PsA and AS patients, at less than one in 1000 person–years. Indeed, in Swedish PsA and AS patients there were 0.59 and 0.40 incidences per 1000 person–years in exposed versus unexposed patients, while the corresponding values were 0.87 and 0.19 in the Danish cohort.
Furthermore, there were 0.37 and 0.39 incidences of neuroinflammatory diseases per 1000 person–years in the exposed versus unexposed Swedish RA patients, and 0.39 versus 0.28 incidences per 1000 person–years in the Danish patients.
An “on-drug” analysis revealed a slightly lower risk for neuroinflammatory diseases than the main analysis, which Kopp and team explain “may suggest that demyelinating events develop after long exposure time, and even after treatment has been discontinued.”
Writing in the Annals of the Rheumatic Diseases, the researchers conclude that “the use of TNF [inhibitors] for the treatment of PsA or AS, but not for RA, may be associated with increased risk of having a demyelinating disease or inflammatory neuropathy,” and they say this should be acknowledged in clinical risk analyses.
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