Risk of cardiovascular and autoimmune disease in people with multiple sclerosis on long-term interferon-β therapy

Chronically elevated type I interferons (-β and -α) can induce atherosclerosis and autoimmunity but whether this link translates into adverse events in interferon-β users with multiple sclerosis is unknown. We therefore aimed to determine whether long-term interferon-β exposure increases the risk of cardiovascular and autoimmune disease in a Canadian population-based cohort with linked hospital/physician visits and filled prescriptions. People with multiple sclerosis were included from the most recent of i) first diagnostic code or disease-modifying therapy or ii) prescription data availability (1/JAN/1996), and followed until the earliest of outcome, emigration, death or study end (31/DEC/2017). Associations were tested using stratified Cox regressions with time-dependent covariates. The cohort included 19,360 people with multiple sclerosis followed for a median duration of 11.2 years (Q1-Q3: 5.1-18.7), of whom 3,138 (16.2%) ever used an interferon-β. Longer interferon-β therapy was associated with a higher incidence of cardiovascular disease (per 5-year longer treatment: hazard ratio=1.18; 95% confidence interval: 1.02, 1.37; p=0.026) but not with autoimmunity (hazard ratio=0.74; 95% confidence interval: 0.49, 1.11; p=0.139). This new safety signal should encourage clinicians to optimise cardiovascular prevention in people with multiple sclerosis and may be considered when discussing treatment options in interferon-β users who are at high risk or with established cardiovascular disease.