Antitumor necrosis factor alpha (TNF-alpha) inhibitors are associated with an increased risk of multiple sclerosis (MS), especially among patients with rheumatic disease (RD), new research shows.
When researchers combed medical databases from four Canadian provinces for information on patients with DR and irritable bowel disease (IBD) taking anti-TNF-alpha agents along with matched controls in a prospective cohort study, they find an increased risk of MS in patients with DR.
Dr. Antonio Aviña-Zubieta
Physicians should not hesitate to prescribe anti-TNF-alpha therapy to patients if they believe their patients may benefit from it, study investigator Antonio Aviña-Zubieta, MD, PhD, senior scientist, told Medscape of Arthritis Research Canada in Vancouver, British Columbia. Medical news.
“To better provide context for the magnitude of the risk, we would need to treat 2,268 people with anti-TNF-alpha therapy to get one additional case of MS. This is considered a rare side effect. [of anti-TNF therapy]” he said, adding that MS still occurred even in people who did not receive anti-TNF therapy.
“However, we do not recommend anti-TNF in patients with MS or with a family history of MS. The decision to take anti-TNF is best made jointly by the patient and the healthcare provider,” said Aviña-Zubieta.
The study was published online Oct. 28 in the journal Neurology.
The potential link of MS has been investigated
Anti-TNF-alpha agents are often prescribed to stop inflammation in chronic immune disorders such as rheumatoid arthritis, inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis. Previous research has raised suspicions of an increased risk of MS with the use of anti-TNF-alpha agents in small samples.
The researchers accessed population-linked databases in the Canadian provinces of British Columbia, Alberta, Saskatchewan and Manitoba, which contain information on doctor visits, hospitalizations, demographics and medications in those provinces.
They mined the databases for information on patients diagnosed with DR and IBD between January 2000 and March 2018 and then determined new incident MS cases in both disease cohorts with at least three MS-related outpatient records , hospitalizations or prescription claims for MS. Researchers could only obtain information on RD from BC and Manitoba databases.
Anti-TNF-alpha drugs were dispensed during the 2 years before MS onset and included adalimumab, certolizumab, etanercept, infliximab, and golimumab.
Each MS case was matched with up to five age-matched control subjects who did not receive anti-TNF-alpha agents, had a similar duration of RD or IBD disease, and the same approximate place of residence.
The researchers identified nearly 300,000 patients with DR. During follow-up, 462 of them developed MS (80% female, mean age 47) and were matched with 2300 controls with DR (60% female, mean age 47). They found that 18 people with DR and MS took an anti-TNF-alpha, compared with 42 of 2296 patients who had DR but not MS.
After adjusting for variables that could influence the risk of developing MS, the researchers found that people with DR who took an anti-TNF-alpha agent had a 105% higher risk of developing MS compared to people with DR who were not taking an anti-TNF-alpha. – TNF-alpha agent.
Aviña-Zubieta said that people with RD who have a family history of MS would be advised against using anti-TNF agents, as there are other medications that could also be helpful.
The researchers observed a smaller increase in the risk of MS in the IBD group, but the findings did not reach statistical significance.
There are several theories as to how anti-TNF therapy may put MS at risk in certain patients. Aviña-Zubieta speculated that the therapy may increase the reactivity of immune cells to myelin causing loss and malfunction in affected areas. In addition, “blockade of TNF by this therapy may affect myelin repair. The possibility of an increased risk of infections that could be related to MS is also possible, but not proven,” he noted.
Study limitations included smaller sample sizes from Saskatchewan and Manitoba. The researchers also noted that MS prodrome periods can occur up to 5 years before onset, so patients with early MS symptoms or an MS prodrome that has not yet been diagnosed may be misdiagnosed as controls.
Context is important
Commenting on the study for Medscape Medical News, Dr. Amy Kunchok, a neurologist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, Cleveland, Ohio, said context is important when interpreting the findings. .
Dr. Amy Kunchok
“Anti-TNF therapies are very effective for many autoimmune disorders, as evidenced by numerous randomized controlled trials in rheumatologic disorders and IBD,” said Kunchok, who was not involved in the study.
“As with any therapeutic decision, the physician must consider the patient’s medical needs and the risk-benefit scenario. In a patient with a preexisting diagnosis of MS, we would generally not recommend these therapies, but instead suggest that the treatment specialist consider alternatives.
“However, in patients without prior inflammatory neurological disorders, these therapies can be safe and effective. More work is needed to risk-stratify patients in terms of these rare CNS inflammatory events,” he added.
neurology Published online October 28, 2022. Abstract
The study was funded by the Canadian Institutes of Health Research. Aviña-Zubieta and Kunchok report no relevant financial relationships.
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