TNFα-inhibitor biologics for rheumatic disease linked to the development of MS

A new Canadian study has compared the risk of developing multiple sclerosis (MS) in patients with rheumatic disease or inflammatory bowel disease being treated with tumour necrosis factor alpha (TNFα) inhibitors. Anti-TNFα medications (e.g., infliximab, adalimumab, etanercept, golimumab, and certolizumab) have been consistently proven effective in improving patients’ quality of life, as well as preventing joint and tissue damage, disability and premature death. To date, an increased risk of MS with the use of these biologic agents has been suggested, but studies have been limited.1 To further examine this issue, investigators from Arthritis Research Canada conducted a nested case-control study using population-based healthcare linked databases from four Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba). All patients with rheumatic disease or inflammatory bowel disease living within one of the four participating provinces between January 2000 and March 2018 were identified.1 The investigators also identified any anti-TNFα agents dispensed in the two years prior to onset of MS. 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 after adjusting for potential confounders. A meta-analysis was conducted to provide pooled estimates across provinces using random-effects models.1 Results showed the following: Among 296,918 individuals with rheumatic disease, 462 people developed MS (80.1% female, mean age, 47.4 years). The 462 people with rheumatic disease and MS were matched with 2,296 controls (59.5% female, mean age, 47.4 years). Exposure to anti-TNFα agents occurred in 18 individuals with rheumatic disease and MS, and 42 controls. After adjusting for important variables that could influence the risk of developing MS, the pooled incidence rate ratio was 2.05 (95% CI, 1.13–3.72). Among 84,458 patients with inflammatory bowel disease, 190 MS cases (69.5% female, mean age, 44.3 years) were matched with 943 controls (54.1% female, mean age, 44.2 years). Exposure to anti-TNFα agents occurred in 23 individuals with inflammatory bowel disease and MS, and 98 controls. The pooled adjusted incidence rate ratio was 1.35 (95% CI, 0.70–2.59). This association was not statistically significant.1 Read: Major adverse cardiovascular events associated with tofacitinib in the treatment of RA The authors conclude that in this study, the use of anti-TNFα agents was associated with an increased risk of MS compared to nonusers, and the risk was higher among patients with rheumatic disease compared to those with inflammatory bowel disease.1 To put this risk in perspective, the authors calculated the number needed to harm; 2,268 people with rheumatic disease would need to take an anti-TNFα agent in order for one person to get MS.2,3 The investigators believe these findings will help clinicians and patients with rheumatic disease make more informed treatment decisions. Further studies are needed to validate these results for patients with inflammatory bowel disease.1,2 Read: Health Canada releases advisory on risks of JAK inhibitors In a press release accompanying the online publication of the study results, Dr. J. Antonio Aviña-Zubieta, a senior scientist at Arthritis Research Canada and one of the study’s authors, stated that “People with rheumatic disease who have a family history of multiple sclerosis should not be taking these drugs; there are other drug options. However, because the risk is very rare, for those without a family history of multiple sclerosis the benefits of anti-TNFα [agents] for managing rheumatic disease outweigh the risks.”2 References 1. Li L, Aviña-Zubieta JA, Bernstein CN, et al. Risk of multiple sclerosis among users of antitumor necrosis factor alpha in four Canadian provinces: a population-based study. Neurology 2022; published online October 28, 2022. https://n.neurology.org/content/early/2022/10/28/WNL.0000000000201472 (accessed November 16, 2022). 2. Arthritis Research Canada. Research links TNF biologics use with risk of multiple sclerosis. Vancouver, BC; November 1, 2022. https://www.arthritisresearch.ca/tnf-biologics-ms-risk/ (accessed November 16, 2022). 3. Strijbis EMM, Koch MW. TNF alfa blockers and the risk of multiple sclerosis. Neurology 2022; published online October 28, 2022. DOI: 10.1212/WNL.0000000000201629.

TNFα-inhibitor biologics for rheumatic disease linked to the development of MS

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