When researchers combed medical databases in four Canadian provinces for information on patients with DM and irritable bowel disease (IBD) taking anti-TNF-alpha agents along with matched controls in a prospective cohort study, they found an increased risk of MS in patients with DM. 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 researcher Antonio Aviña-Zubieta, MD, PhD, senior scientist at Arthritis, told Medscape Research Canada in Vancouver, British Columbia. Medical News. “To better provide a context of the magnitude of the risk, we would need to treat 2268 people with anti-TNF-alpha therapy in order to have one additional case of multiple sclerosis. This is considered a rare side effect [of anti-TNF therapy],” he said, adding that MS still occurs even in people who did not receive anti-TNF therapy. “However, we do not recommend anti-TNFs in patients with multiple sclerosis or those with a family history of multiple sclerosis. The decision to take anti-TNFs 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.

A possible MS connection was investigated

Anti-TNF-alpha agents are often prescribed to stop inflammation for chronic immune disorders such as rheumatoid arthritis, inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis. Previous research has suspected 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 about doctor visits, hospitalizations, demographics and medications in those provinces. They mined the databases for information on patients diagnosed with DM and IBD between January 2000 and March 2018, and then identified new MS cases in the two disease groups with at least three MS-related outpatient records, hospitalizations, or MS prescription claims. Researchers could only obtain information on RD from databases in BC and Manitoba. Anti-TNF-alpha drugs were dispensed in the 2 years before MS onset and included adalimumab, certolizumab, etanercept, infliximab, and golimumab. Each MS case was matched with up to five control subjects of similar age who did not receive anti-TNF-alpha agents, had similar disease duration of RD or IBD, and the same approximate place of residence. The researchers identified nearly 300,000 patients with DM. During follow-up, 462 of them developed MS (80% women, mean age 47 years) and were matched with 2300 controls with RD (60% women, mean age 47 years). They found that 18 people with DM and MS received an anti-TNF-alpha, compared with 42 of 2296 patients who had DM but no MS. After adjusting for variables that could affect the risk of developing MS, the researchers found that people with DM who received an anti-TNF-alpha agent had a 105% increased risk of developing MS compared with people with DM who did not receive anti- TNF-alpha factor. Aviña-Zubieta said it would not be good for people with DM who have a family history of MS to use the anti-TNF agents, as there are other drugs that could also be helpful. The researchers observed a smaller increased risk for MS in the IBD group, but the findings did not reach statistical significance.
There are several theories about how anti-TNF therapy may be a risk for MS in some patients. Aviña-Zubieta hypothesized that the treatment may increase reactivity from immune cells to myelin, leading to loss and dysfunction of the affected areas. Additionally, “TNF blockade by this treatment may interfere with myelin repair. The possibility of a higher risk of infections that could be linked to multiple sclerosis is also possible, but not proven,” he noted. Study limitations included smaller sample sizes from Saskatchewan and Manitoba. The researchers also noted that pre-MS episodes can occur up to 5 years before onset, so patients with early symptoms of MS or MS that have not yet been diagnosed may be misdiagnosed as controls.

Context is important

Commenting on the study for Medscape Medical News, Amy Kunchok, MD, a staff neurologist at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis in Cleveland, Ohio, said context is important when interpreting the findings. Dr. Amy Kunchok “Anti-TNF therapies are highly effective for many autoimmune disorders, as demonstrated by numerous randomized controlled trials in rheumatologic disorders and IBD,” said Kunchok, who was not involved in the study. “As with any treatment decision, the physician must consider the patient’s medical needs and the risk-benefit scenario. In a patient with a pre-existing diagnosis of MS, we would generally not recommend these treatments, but instead suggest that the treating specialist consider alternatives . “However, in patients without prior inflammatory neurological disorders, these treatments may be safe and effective. More work is needed to stratify patients for 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. For more Medscape Neurology news, join us on Facebook and Twitter