Association of Oral Disease-modifying Agents and Their Adherence Trajectories with Annual Relapses in Multiple Sclerosis

Background Real-world effectiveness can vary across oral disease-modifying agents (DMAs) and their adherence trajectories in patients with multiple sclerosis (MS). However, previous studies have not considered longitudinal adherence patterns while evaluating oral DMAs. Objectives This study aimed to evaluate the association of oral DMAs and their adherence trajectories with annualized relapse rate (ARR) in patients with MS. Methods This retrospective observational cohort study based on the 2015-2019 IBM MarketScan Commercial Claims and Encounters Database involving adults (18-64 years) identified with ≥1 MS diagnosis (ICD-9/10-CM:340/G35) and ≥ one oral DMA prescription with continuous insurance enrollment. Patients were grouped into incident fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users based on the index DMA with a one-year washout period. Annual DMA adherence trajectories based on the monthly Proportion of Days Covered (PDC) one year after treatment initiation were identified using Group-Based Trajectory Modeling (GBTM). Relapses were evaluated using the validated claims-based algorithm. The ARR was measured during the one-year follow-up period. Results The study cohort consisted of 994 MS patients who initiated with FIN (23.0%), TER (22.3%), and DMF (54.7%) during the study period. The GBTM grouped eligible patients into three adherence trajectories: complete adherers (58.2%), slow decliners (24.5%), and rapid decliners (17.4%). The proportion of complete adherers varied across the oral DMAs (FIN: 66.7%, TER: 55.4%, and DMF: 57.4%). Generalized boosted model-based inverse probability treatment weights with negative binomial regression modeling revealed that, while there was no difference in ARR across the three DMAs, rapid decliners (adjusted incidence rate ratio[aIRR]: 1.6, 95% CI: 1.1-2.4) had a higher rate of relapses compared to completely adherent patients. The type of oral DMAs did not moderate the relationship between ARR and the adherence trajectory groups. Conclusions Adherence trajectories classified as rapid decliners were associated with a higher ARR than complete adherers after adjusting for their type of oral DMAs. Longitudinal medication adherence patterns are critical in reducing relapse rates in MS.