The excessive number of deaths in placebo-treated patients largely was the result of MS-related causes, especially MS-related pulmonary infections.
The rate of all-cause mortality in patients with multiple sclerosis (MS) was greater in those who received placebo than in those who received active treatment in a randomized controlled trial of interferon (IFN) Î²-1b therapy conducted 2 decades ago. In a long-term follow-up of the pivotal randomized controlled trial, the researchers found that the excessive number of deaths in the placebo-treated patients largely was the result of MS-related causes, especially MS-related pulmonary infections.1
Patients with MS die, on average, 7 to 14 years prematurely compared with controls, noted researchers in the department of neurology at the University of California, San Francisco. They previously reported that 21 years after participation in the pivotal trial of IFNÎ²-1b, mortality was reduced by 46% to 47% in the 2 groups who received active therapy during the trial.
The investigators conducted the long-term follow-up study to analyze the causes of death in these 3 randomized patient cohorts. They used multiple information sources to determine whether the excessive deaths observed in placebo-treated patients was the result of MS-related causes.
Among the 366 patients with MS in the long-term follow-up study, 81 deaths were recorded (mean age at death, 51.7 years). The cause of death or MS relationship or both were determined for 88% of deaths. Patients were assigned to 1 of 9 cause of death categories: cardiovascular disease/stroke, cancer, pulmonary infections, sepsis, accidents, suicide, death resulting from MS, other known cause of death, and unknown cause of death.
More than three-fourths (78.3%) of the deaths were determined to be MS-related. The number of MS-related deaths was excessive in the patients who were randomized to receive placebo during the randomized controlled trial compared with controls.
The authors noted that the question of whether the impact of therapy on mortality is the consequence of early treatment or a larger cumulative exposure to IFNÎ²-1b cannot be resolved. However, they suggested that the data support the notion that the mortality benefit from IFNÎ²-1b is the result of a treatment-related impact on the MS disease process.
1. Goodin DS, Ebers GC, Cutter G, et al. Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNÎ²-1b study. BMJ Open. 2012 Nov 30;2. Read full article here.