Adherence to Disease Modifying Agents (DMAs) is vital for disease management of Multiple Sclerosis (MS). The route of administration of DMA is one of the important factors associated with adherence in general and MS in specific. With the advent of oral DMAs in the last decade, the landscape of DMA treatment has changed significantly. Oral DMAs offer convenience in administration and offer other benefits over conventional injectable DMAs. Most of the previous studies assessed annual DMA adherence as a point estimate using medication possession ratio or proportion of days covered which failed to account for time-related changes in the adherence patterns over time. The Group-Based Trajectory Modeling (GBTM) classifies individuals into different adherence trajectory groups based on the prescription-filling pattern over time. Our preliminary analyses involving 2010- 2012 MarketScan revealed that oral fingolimod was associated with higher odds of being a complete adherer (Odds Ratio (OR): 2.78, 95% Confidence Interval (CI):1.85-4.16) or a slow discontinuer (OR: 2.62, 95% CI: 1.70- 1.05) relative to injectable DMA. In the past decade, several other new oral DMAs were introduced to treat MS, such as teriflunomide and dimethyl fumarate. These oral DMAs differ in their treatment regimen and may have consequences with respect to adherence and relapse. However, there is no real-world evidence regarding the adherence patterns over time and associated relapse rates with oral DMAs in MS. Therefore, the overall goal of this research is to evaluate adherence trajectories of oral DMAs over time and associated outcomes in MS patients. The specific aims of this study are: (1) to evaluate DMA adherence trajectory patterns of oral DMAs in MS; and (2) to evaluate the effect of adherence trajectories on relapse rates in MS. This study tests the following hypotheses- (i) adherence trajectory patterns differ across different oral DMAs, and (ii) patients with better adherence trajectories will have lower relapse rates. This retrospective observational study will involve adults with MS, with incident oral DMA use from the 2016-2018 MarketScan. The oral DMAs will involve three agents, namely, fingolimod, teriflunomide, and dimethyl fumarate. Relapse will be defined as inpatient hospitalization or an outpatient visit with a corticosteroid prescription within 30 days. The novel GBTM will involve finite mixture modeling for approximating adherence trajectories of oral DMA use over a one-year period. The study will adjust for selection bias within the multivariable context of the Andersen Behavioral Model. Multinomial regression using Inverse Probability Treatment Weights (IPTW) based on Generalized Boosted Models (GBM) will be used to evaluate trajectory patterns across different oral DMAs. Poisson regression models with IPTW based on GBM will be used to evaluate the relapse rates across oral DMAs with variable adherence trajectories. The study findings will provide valuable re...