TNF inhibitors in PsA, ankylosing spondylitis linked to higher neuroinflammatory risk
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Treatment with TNF inhibitors is associated with an increased — albeit still low — risk for neuroinflammatory disease in patients with ankylosing spondylitis and psoriatic arthritis, but not rheumatoid arthritis, according to data published in the Annals of the Rheumatic Diseases.
“Several case reports and small case series have indicated that treatment with TNFi treatment may be linked with neuroinflammatory disorders, for example, multiple sclerosis (MS), inflammatory neuropathies and optic neuritis,” Tine Iskov Kopp, MSc, PhD, of the Danish Multiple Sclerosis Registry, Rigshospitalet Glostrup, and colleagues wrote.
“To examine whether such neuroinflammatory events are merely coincidental or causally linked to the use of TNFi, and how any association may vary by treatment indication, large observational studies with sufficiently long follow-up are warranted,” they added. “To date, only a few observational studies exist, mostly pointing toward increased risk of neuroinflammatory adverse events following TNFi treatment.”
To determine whether TNF inhibitors are linked to an increased risk for neuroinflammatory diseases in patients with arthritic conditions, Kopp and colleagues conducted a prospective cohort study in Denmark and Sweden. Patients with inflammatory arthritis were identified using the Danish DANBIO and the Anti-Rheumatic Treatment in Sweden national registers. Data from Denmark included adult DANBIO participants diagnosed with RA, PsA or AS who began TNF-inhibitor treatment between Jan. 1, 2000, and Jan. 20, 2017. Data from the Swedish registry included adults with the same diseases who started TNF-inhibitor from Jan. 1, 2000, to Dec. 29, 2017.
Kopp and colleagues included 25,796 patients with RA, 8,586 with PsA and 9,527 with AS who initiated TNF inhibitors in their analysis. The study included 175,520 total patients with arthritic diseases. Data on demyelinating disease and inflammatory neuropathy diagnoses were gathered from prospective linkage to the National Patients Register. The researchers used a Cox proportional hazard model to compare those treated with TNF inhibitors and those who were not, based on disease and country.
The researchers identified 270 events of neuroinflammatory diseases in Sweden, and 51 in Denmark, among 111,455 total patients with RA. This corresponded to crude incidence rates of 0.37 per 1,000 person-years in Sweden, and 0.39 per 1,000 person-years in Denmark, among patients treated with TNF inhibitors (Swedish HR = 0.97; 95% CI, 0.72-1.33; Danish HR = 1.45; 95% CI, 0.74-2.81), compared with 0.39 and 0.28, respectively, in unexposed patients.
Among the 64,065 total patients with AS or PsA, there were 196 and 32 neuroinflammatory disease, respectively, representing crude incidence rates of 0.59 and 0.87 among patients treated with TNF inhibitors (Swedish HR = 1.5; 95% CI, 1.07-2.11; Danish HR = 3.41; 95% CI, 1.3-8.96), compared with 0.4 and 0.19 in unexposed patients. Hazard ratio patterns were similar for multiple sclerosis, the researchers wrote.
“Our study adds nationwide, real-world evidence from two countries to a long-standing issue of concern about treatment with TNF inhibitors,” Kopp told Healio Rheumatology. “Treatment with TNF inhibitors is associated with increased risk of neuroinflammatory disorders as a rare side effect — absolute risk is below one in 1,000 patients per year — among patients with psoriatic arthritis and ankylosing spondylitis — but not with rheumatoid arthritis.”
She added, “The risk profile following treatment with TNF inhibitors may be different for inflammatory arthritides and we therefore recommend that treating rheumatologists pay attention to neurological symptoms during treatment with TNF inhibitors — especially among patients with psoriatic arthritis and ankylosing spondylitis.” – by Jason Laday
Disclosure: Kopp reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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