Mortality outcomes for interferon beta-1b versus placebo 21 years following randomization

Objective: To assess the effect of interferon beta‐1b (IFNB‐ 1b) 250 mug on mortality outcomes in multiple sclerosis (MS). Methods: Originally 372 patients were randomized to either IFNB‐1b 50 mug (n = 125), IFNB‐1b 250 mug (n = 124), or placebo (n = 123), and remained on assigned treatment for a median 3.8 years (maximum 5.1 years), before licensed treatment became available. The primary outcome variable in this 21 year follow‐up study was allcause mortality and the secondary cause‐specific mortality. Results: At 21.1 years (median), vital status information was available for 366/372 (98.4%) of patients; of whom, 81 (22.1%, 81/366) were deceased. Original randomization to IFNB‐1b 250 mug showed a significant reduction in all‐cause mortality versus placebo (log‐rank test, P = 0.0272) and risk of death was reduced by 39.3%. Cause of death data was assessed for 75% of deaths; of which, 50/61 (82%) were MS‐related. Most of the excess mortality rate in placebo was MS‐related. Conclusions: With near‐complete ascertainment and over 21 years of observation time, a substantial survival advantage was seen for patients receiving early IFNB‐1b treatment versus placebo. Most of this striking difference appears to be due to MS‐related deaths.