Multiple sclerosis (MS) is a chronic, neurodegenerative disease with a reported 10.4% increase in global prevalence between 1990 and 2016, to over 2.2 million cases. 1,2 While there is no cure for MS, disease-modifying therapies (DMTs), 3,4 reduce annualized relapse rates by 18.0% to 66.0% 5,6 and disability progression by 12.0% to 41.0%. 6 Optimal medication adherence is crucial to maximize drug efficacy and reduce unnecessary healthcare expenditure. However, World Health Organization 7 data estimates approxmimately 50% of people with chronic diseases experience suboptimal medication adherence. Medication adherence in MS is no exception. Adherence rates for selfinjectable DMTs are reported as between 41% to 88% across varying measurement types, 8 and between 30% to 60% of people with MS discontinue self-injectable DMTs within two years. [9][10][11] The introduction of oral DMTs has not resolved the problem. A study assessing one-year adherence and persistence to oral DMTs-fingolimod (FTY), teriflunomide (TFN), and dimethyl fumarate (DMF)-reported that the adherence rate, measured by proportion of days covered (PDC), was less than 80% in 24.6% to 46.9% of participants with discontinuation rates between 25.6% to 50.3%. 12 Studies consistently showed an increased likelihood of suboptimal medication adherence or discontinuation with increasing treatment durations. [13][14][15] Medication adherence is "The extent to which a patient acts in accordance with the prescribed interval, and dose of a dosing regimen." 16 Persistence is "The duration of time from initiation to discontinuation of therapy." 16 Discontinuation is the cessation of therapy, which may be initiated by either the clinician or patient. 17 Suboptimal medication adherence may be intentional or unintentional. Intentional suboptimal adherence has been linked to perceived inefficacy, 18 cost, 19 and medication side effects. Side effects vary by DMT, but they may include fatigue, headache, nausea, or diarrhea. Specific to route of administration, injectable DMTs may incur injection site reactions and needle phobia. 3 Forgetting is the most common unintentional reason for suboptimal medication adherence. Factors such as physical disability, cognitive impairment, and depression-all common in MS patients-contribute to medication adherence difficulties. 3,18 Medication adherence may be assessed objectively, using, for example, pharmacy records, or via patient self-report.Two previous systematic reviews have been undertaken addressing medication adherence and persistence to selfadministered injectable DMTs in people with MS, 8,15 both of which predated studies that assessed medication adherence and persistence in oral DMTs. Two recent reviews of oral DMT adherence and discontinuation rates did not compare oral and injectable DMTs to quantify whether oral ABSTRACT BACKGROUND: Medication adherence is critical for the realization of pharmacotherapy benefits and reduced healthcare expenditure. Studies have shown up to 60% of people with Multiple sclerosis (MS) exper...