PROJECT SUMMARY/ABSTRACT Disease Modifying Agents (DMAs) are vital for reducing inflammation and limiting disease activity in multiple sclerosis (MS). However, there is a decline in inflammation and disease activity in older adults with MS due to natural disease progression. In fact, most patients with MS over age 65 have very limited disease activity and relapses. DMAs are not effective in preventing disability and disease progression associated with aging. There is also very limited data on the effectiveness of DMAs in older adults with MS. Also, DMA use is associated with increased infections, malignancy, and other adverse events. Continued DMA use in older adults is highly debated due to no proven efficacy, safety concerns, and high prescription costs. Therefore, there is an urgent need to evaluate the benefits and safety of DMA discontinuation in older adults. Although some studies with limited samples found preliminary evidence for DMA discontinuation, no large-scale pharmacoepidemiological study evaluated both the safety and effectiveness of DMA deprescribing in older adults. Our previous based study found that older adults with MS received injectables (55%), followed by orals (32%). However, over 35% of older adults discontinued their DMAs after 12 months. The overall goal of this research is to evaluate deprescribing and associated effectiveness and safety outcomes in older adults with MS. The specific objectives of the research are to: (1) examine DMA use and deprescribing in older adults with MS; (2) evaluate the effect of DMA deprescribing on relapse rates and frailty; and (3) evaluate the effect of DMA deprescribing on serious infections and all-cause mortality in older adults with MS. This study will involve a longitudinal national cohort of older adults over 65 years of age with MS and DMA use based on ten-year Medicare claims data involving Parts A, B, and D. The study will test the hypotheses that (i) there is no difference in relapse rates and frailty in older adults who are deprescribed and those who continue DMA, (ii) and DMA deprescribing is associated with decreased infection rates and all-cause mortality in older adults with MS. Deprescribing will be defined as the discontinuation of DMAs for at least 12 months with a one-year baseline adherence of DMAs (proportion of days covered of >0.80). The comparator group will be those continuing their DMAs. The relapse rates and frailty will be operationalized using validated claims-based algorithms. The risk of serious infections and specific types of infection, along with mortality, will also be evaluated. The study will involve a propensity score-matched cohort design based on generalized boosted models to adjust for the selection bias within the multivariate context of the Andersen Behavioral Model. Multivariable models within propensity score-matched sets will be used to evaluate the effectiveness and safety outcomes. Multiple sensitivity analyses involving differing analytical...