CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study

Hutto, Spencer K.; Rice, Dylan R.; Mateen, Farrah J.

doi:10.1016/j.jneuroim.2021.577587

Cited by 14 publications

(4 citation statements)

References 28 publications

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“…7 In some cases, demyelination was identified in patients prior to the use of anti-TNF medications, which suggests that they did not cause the demyelination but unmasked a pre-existing disease. 8 For monitoring and surveillance, MRI scans after the initiation of anti-TNF therapy may be performed on a regular basis in order to detect early changes in asymptomatic patients. In our patient, a baseline brain MRI was not performed since it is not part of the required workup prior to the initiation of adalimumab and she did not have any neurological symptoms prior to the initiation of the medication.…”

Section: Discussionmentioning

confidence: 99%

Adalimumab-induced central nervous system demyelination in a patient with rheumatoid arthritis

et al. 2023

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Adalimumab (Humira) is a human monoclonal antibody that belongs to the tumor necrosis factor (TNF) alpha antagonist class of medications. Central Nervous System (CNS) demyelination is a rare side effect of adalimumab, and only a few cases have been reported in the literature of patients who developed multiple sclerosis or other demyelinating patterns after using adalimumab. In this report, we present a case of CNS demyelination in a patient with rheumatoid arthritis that developed a few months after using adalimumab. Performing brain MRI for asymptomatic individuals prior to initiating anti-TNF alpha agents to exclude a pre-existing demyelinating disease may be worthwhile. Routine brain MRI for monitoring and surveillance may facilitate detecting cases early and avoid the development of permanent neurological disability. Further studies are needed to clarify the neurological safety of anti-TNF alpha agents.

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Section: Discussionmentioning

confidence: 99%

Adalimumab-induced central nervous system demyelination in a patient with rheumatoid arthritis

et al. 2023

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“…Anti-tumor necrosis factor alpha (TNFα) agents have been shown to significantly improve the quality of life in patients with several chronic immune-mediated inflammatory diseases [1]. However, an increased risk of multiple sclerosis (MS) or demyelinating events has been suspected after their use [2][3][4][5][6]. One of the first studies that postulated an association between anti-TNFα and MS pathogenesis was a randomized trial which was stopped early due to an increased rate of MS exacerbation among patients who received the drug lenercept [7].…”

Section: Introductionmentioning

confidence: 99%

Multiple sclerosis risk among anti-tumor necrosis factor alpha users: A methodological review of observational studies based on real-world data

Etminan

Kaplan

et al. 2022

Preprint

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Epidemiologic studies on the risk of multiple sclerosis (MS) or demyelinating events associated with anti-tumor necrosis factor alpha (TNFα) use among patients with rheumatic diseases or inflammatory bowel diseases have shown conflicting results. Causal directed acyclic graphs (cDAGs) are useful tools for understanding the differing results and identifying the structure of potential contributing biases. Most of the available literature on cDAGs uses language that might be unfamiliar to clinicians. This article demonstrates how cDAGs can be used to determine whether there is a confounder, a mediator or collider-stratification bias and when to adjust for them appropriately. We also use a case study to show how to control for potential biases by drawing a cDAG depicting anti-TNFα use and its potential to contribute to MS onset. Finally, we describe potential biases that might have led to contradictory results in previous studies that examined the effect of anti-TNFα and MS, including confounding, confounding by contraindication, and bias due to measurement error. Clinicians and researchers should be cognizant of confounding, confounding by contraindication, and bias due to measurement error when reviewing future studies on the risk of MS or demyelinating events associated with anti-TNFα use. cDAGs are a useful tool for selecting variables and identifying the structure of different biases that can affect the validity of observational studies.

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“…Although anti-TNFα agents are generally well-tolerated and have been shown to significantly improve patients' quality of life, [3][4][5][6] an increased risk of MS has been suspected after their use. [7][8][9][10][11] One of the first studies that postulated an association with MS pathogenesis was a randomized controlled trial that was stopped early because of an increased MS exacerbation rate among lenercept-treated patients. 12 Epidemiologic data suggesting anti-TNFα use may trigger new onset MS are scarce and contradictory, [13][14][15][16][17] mainly because of potential biases such as sparse data bias.…”

mentioning

confidence: 99%

“…Although anti-TNFα agents are generally well-tolerated and have been shown to significantly improve patients' quality of life, 3-6 an increased risk of MS has been suspected after their use. 7-11…”

mentioning

confidence: 99%

Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces

Aviña‐Zubieta

Bernstein

et al. 2023

Neurology

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Background and Objectives:Anti-tumor necrosis factor alpha (TNFα) agents are a class of biologic drugs used for the treatment of several immune-mediated conditions. An increased risk of multiple sclerosis (MS) with their use has been suggested, but studies have been limited. Relevant population-based epidemiologic data linking anti-TNFα to MS are scarce. To compare the risk of MS in anti-TNFα users with non-users among rheumatic disease (RD) or inflammatory bowel disease (IBD) patients.Methods:A nested case-control study was conducted. Population-based healthcare linked databases from four Canadian provinces were used. All patients with RD or IBD residing within a participating province between January 2000 and March 2018 were identified by validated case definitions. Any anti-TNFα dispensation in the two years prior to the index date (MS onset) was identified. Incident-onset MS cases were ascertained using a validated algorithm. Up to five controls were matched to each MS case based on birth year ±3 years, disease duration, and health authority (based on region of residence). Conditional logistic regressions were used to calculate the incidence rate ratio (IRR) after adjusting for potential confounders. A meta-analysis was conducted to provide pooled estimates across provinces using random-effects models.Results:Among 296,918 RD patients, 462 MS cases (80.1% female, mean [SD] age, 47.4 [14.6] years) were matched with 2,296 controls (59.5% female, mean [SD] age, 47.4 [14.5] years). Exposure to anti-TNFα occurred in 18 MS cases and 42 controls. After adjusting for matching variables, sex, and the Charlson Comorbidity Index, the pooled IRR was 2.05 (95% CI, 1.13-3.72). Among 84,458 IBD patients, 190 MS cases (69.5% female, mean [SD] age, 44.3 [12.3] years) were matched with 943 controls (54.1% female, mean [SD] age, 44.2 [12.2]). Exposure to anti-TNFα occurred in 23 MS cases and 98 controls. The pooled adjusted IRR was 1.35 (95% CI, 0.70-2.59).Discussion:The use of anti-TNFα was associated with an increased risk of MS compared to non-users, especially among patients with RD. These findings could help clinicians and patients with RD to make more informed treatment decisions. Further studies are needed to validate these results for IBD patients.

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CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study

Cited by 14 publications

References 28 publications

Adalimumab-induced central nervous system demyelination in a patient with rheumatoid arthritis

Adalimumab-induced central nervous system demyelination in a patient with rheumatoid arthritis

Multiple sclerosis risk among anti-tumor necrosis factor alpha users: A methodological review of observational studies based on real-world data

Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces

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