Abstract
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 3138 (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 optimize 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.