Disclosures: Kunchok reports research funding from Biogen. Please see the full study for all other authors’ relevant financial disclosures.
June 24, 2020
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TNF inhibitors linked to greater risk for inflammatory central nervous system events

Disclosures: Kunchok reports research funding from Biogen. Please see the full study for all other authors’ relevant financial disclosures.
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The use of TNF inhibitors among patients with autoimmune disease may be associated with an increased risk for inflammatory central nervous system events, according to data published in JAMA Neurology.

“After the introduction of TNF inhibitors, several studies reported an association between TNF inhibitors and inflammatory demyelinating central nervous system (CNS) events such as optic neuritis, transverse myelitis and multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD),” Amy Kunchok, MBBS, MMed, of the Mayo Clinic, in Rochester, Minn., and colleagues wrote.

The use of TNF inhibitors among patients with autoimmune disease may be associated with an increased risk for inflammatory central nervous system events, according to data.

“Little is known about the inflammatory non-demyelinating CNS events that occur during TNF inhibitor therapy,” they added. “Case reports have suggested a possible association between non-demyelinating CNS events and neurosarcoidosis, CNS vasculitis, leptomeningitis, or meningoencephalitis.”

To analyze whether treatment with TNF inhibitors is associated with inflammatory demyelinating and non-demyelinating central nervous system events, as well as the spectrum of said events, Kunchok and colleagues conducted a nested case-control study of patients with autoimmune diseases at the Mayo Clinic. The researchers included medical records from 212 patients treated at three Mayo Clinic locations between, Jan. 1, 2003, and Feb. 20, 2019. These included 106 patients with inflammatory central nervous system events and 106 control participants.

Autoimmune diagnoses among the participants included rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn’s disease and ulcerative colitis. Those with diagnostic codes for inflammatory central nervous system events were matched 1:1 with control participants based on birth year, type of autoimmune disease and sex. Data on TNF-inhibitor use, type and duration were collected from medical records. The primary outcome was either an inflammatory demyelinating — multiple sclerosis and other diseases like optic neuritis — or non-demyelinating — meningitis, meningoencephalitis, encephalitis, neurosarcoidosis and central nervous system vasculitis — event.

According to the researchers, treatment with TNF inhibitors occurred in 60% of patients with inflammatory central nervous system events, and in 40% of the control group. As such, the use of TNF inhibitors was associated with an increased risk for any inflammatory central nervous system event, with an adjusted odds ratio of 3.01 (95% CI, 1.55-5.82). Results were similar when stratified by demyelinating and non-demyelinating central nervous system events. The researchers’ secondary analyses determined that the association was predominantly observed in patients with RA (adjusted OR = 4.82; 95% CI, 1.62-14.36).

“In this study population, TNF inhibitor exposure in patients with autoimmune diseases appeared to be associated with an increased risk of both inflammatory demyelinating and nondemyelinating CNS events,” Kunchok and colleagues wrote. “Further research is needed to explore whether this association indicates de novo inflammation or exacerbation of already aberrant inflammatory pathways.”