Informing medication discontinuation decisions among older adults with relapsing-onset multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic neurological condition that persists throughout the life course after onset and has no known cure. Relatively little is known about aging with MS. Medications that target the immune system (disease-modifying treatments [DMDs]) are often burdensome for people with relapsing-onset MS. DMDs are more effective in people who are younger and who have higher disease activity, including relapses, which decreases with age. The potential benefits of DMDs may be low among older adults with relapsing-onset MS. We projected the long-term outcomes of discontinuing DMDs among older adults with relapsing-onset MS. We developed a decision-analytic model that incorporates an age-related decline in relapses and underlying disease heterogeneity (different rates of relapse and disability progression) among simulated individuals. In Paper 1, we estimated the age-related decrease in the annualized relapse rate (ARR) and examined a range of assumptions about the initial ARR at MS symptom onset and the relationship between changes in the ARR, age, and changes in disability status. In Paper 2, we examined the impact of underlying population heterogeneity on the expected outcomes for relapse and disability among older adults who were relapse-free for at least 5 years. Among these cohorts, in Paper 3 we projected the long-term outcomes of continuing versus discontinuing DMDs (interferon beta, fingolimod, or natalizumab) among older adults. We examined different assumptions about treatment efficacy. Outcomes included quality-adjusted life expectancy (QALE), and the percent of a cohort with a relapse or reaching EDSS 6 within the next 10 years.