Sharon Roman[i]
Anti-tumor necrosis factor alpha (anti-TNFα) is a class of drugs derived from human proteins that target the parts of the immune system that trigger inflammation. It is commonly prescribed to treat several chronic autoimmune diseases such as moderate to severe rheumatoid arthritis (RA), ankylosing spondylitis and inflammatory bowel disease (IBD). In general, anti-TNFα medications such as certolizumab, golimumab and etanercept, have been well-tolerated and have significantly improved patients’ quality of life in those with moderate to severe rheumatic diseases. However, their use is suspected to carry an increased risk of multiple sclerosis (MS) onset.
In 2020 an estimated 2.8 million people worldwide were affected with multiple sclerosis; it is one of the world’s most common neurologic disorders. To date, studies suggesting anti-TNFα may trigger MS have been few and contradictory. With increasing rates of both rheumatic diseases and inflammatory bowel disease, the use of this drug, which might have safer, equally effective alternatives, is also expected to rise. The potential risk of MS onset in people already afflicted with a moderate to severe chronic disease, could further increase their burden of disease. This study aimed to measure the risk of MS onset in those being treated with anti-TNFα in people with rheumatic diseases and inflammatory bowel disease.
Results
Across four provinces in Canada, Alberta, British Columbia, Saskatchewan and Manitoba, a total of 296,918 residents with rheumatic diseases (British Columbia and Manitoba) and 84,458 with inflammatory bowel disease (all 4 provinces) were identified in the period between January 2000 and March 2018. Any prescription filled for an anti-TNFα medication 2 years prior to MS onset was identified in these groups. Among the nearly 300,000 patients with rheumatic diseases’, there were 462 MS onset cases (80.1% were female) and 2,2296 without MS (59.5% were female), 18 of the MS cases and 42 without MS were treated with an anti-TNFα medication. Among the inflammatory bowel disease patients, there were 190 MS onset cases (69.5% were female) and 943 without MS (54.1% were female), 23 of the MS cases and 98 of those without MS had been treated with anti-TNFα.
Patients with rheumatic disease or inflammatory bowel disease who developed MS had a higher number of doctors’ visits and hospitalizations, more diseases or conditions at the same time, higher use of medications that fight inflammation, use of prescribed non-steroidal anti-inflammatories (NSAIDs), and use of disease modifying antirheumatic drugs (DMARDs) when compared with those without MS at baseline (i.e., in the year before the anti-TNFα assessment period).
Variables such as sex, region where the person lived, disease duration and age were adjusted for to find the incident rates of MS between anti-TNFα users and non-users. The study authors found that the use of anti-TNFα was associated with an increased risk of MS onset compared to non-users — especially in those with rheumatic diseases; the majority of which occurred within a year of treatment initiation. The treated rheumatic diseases group was 2.05 times more likely to develop MS as the untreated group. Those with inflammatory bowel disease who used anti-TNFα had a 35% increased risk compared to non-users — further studies are needed to investigate the correlation of inflammatory bowel disease and anti-TNFα use with MS to validate these results.
Study demonstrates an increased risk of MS
Until now, data linking anti-TNFα drug use to new onset MS has been scarce. This population-based study is the largest to date and demonstrates an increased risk of MS occurrence among people with rheumatic diseases who use anti-TNFα medications compared to non-users. How anti-TNFα potentially causes MS in those with rheumatic diseases, and possibly inflammatory bowel disease, is not completely understood. Current explanations are varied and include a possible increased risk of demyelination or decrease in myelin repair. Lifestyle factors such as smoking could not be accounted for in this population-based study.
The findings of this study contribute substantially to the understanding of the increased risk of MS with anti-TNFα use and could help doctors and patients with rheumatic diseases who require treatment with an anti-TNFα drug make better informed decisions. In particular, they can weigh the risk versus quality-of-life benefits between the use of an anti-TNFα drug or an alternative, comparable medication not associated with MS.
[i] Vancouver, BC, Canada
Twitter: @SRoman_SPQR
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