Comparative adherence trajectories of oral disease-modifying agents in multiple sclerosis.

Abstract

Oral Disease-Modifying Agents (DMAs) such as fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) are convenient alternatives to injectable DMAs for multiple sclerosis (MS). However, there is limited evidence regarding the comparative adherence patterns of different oral DMAs. This study compared the adherence trajectories between FIN, TER, and DMF users with MS. A retrospective longitudinal study was conducted involving adults (≥18 years) identified with MS (International Classification of Diseases [ICD]-9/10-Clinical Modification [CM]:340/G35) and a DMA prescription from the 2015-2019 IBM MarketScan Commercial Claims Database. Patients were classified as incident FIN-, TER-, or DMF-users based on the index DMA with 1 year of washout period. The DMA adherence trajectories based on the proportion of days covered (PDC) were examined using the Group-Based Trajectory Modeling (GBTM) 1 year after the treatment initiation. Generalized boosting models (GBM)-based Inverse Probability Treatment Weights (IPTW) were incorporated in multinomial logistic regression to assess the comparative adherence trajectories across oral DMAs with FIN group as a reference category. The study cohort consisted of 1,913 patients with MS who were initiated with FIN (24.2%, n=462), TER (24.0%, n=458), and DMF (51.9%, n=993) during 2016-2018. The adherence rate (PDC≥0.8) among FIN, TER, and DMF users was found to be 70.8% (n=327), 59.6% (n=273), and 61.0% (n=606), respectively. The GBTM grouped patients into three adherence trajectories: Complete Adherers-59.1%, Slow Decliners-22.6%, and Rapid Discontinuers-18.3%. The multinomial logistic regression model involving GBM-based IPTW revealed that DMF (adjusted odds ratio [aOR]: 2.32, 95% confidence interval [CI]:1.57-3.42) and TER (aOR: 2.50, 95% CI:1.62-3.88) users had higher odds to be rapid discontinuers relative to FIN users. In addition, TER users were more likely (aOR: 1.50, 95% CI:1.06-2.13) to be slow decliners compared to FIN. TER and DMF were associated with poorer adherence trajectories than FIN. More research is needed to evaluate the clinical implications of these adherence trajectories of oral DMAs to optimize the management of MS.