Evaluation of the Efficacy, Safety, and Adherence to Oral Drug Therapy in Patients with Relapsing–Remitting Multiple Sclerosis

<i>Background and Objectives:</i> Selecting appropriate disease-modifying drugs (DMDs) is crucial for optimizing treatment and slowing disease progression in multiple sclerosis (MS). Real-world studies assess drug efficacy and usage in routine clinical practice. Therefore, the goal of this study was to determine the efficacy and safety of oral drug therapy in patients with relapsing-remitting multiple sclerosis and the particularities of adherence to the therapy. <i>Materials and Methods:</i> A retrospective and prospective study was conducted at the Neurology Clinic of the Kaunas Clinics of the Lithuanian University of Health Sciences. The medical records of patients with relapsing-remitting multiple sclerosis (RRMS) were reviewed. The retrospective study included 286 patients, and the prospective study included 175 patients. <i>Results:</i> The study population included 131 patients on teriflunomide (TFN), 53 on dimethyl fumarate (DMF), 37 on fingolimod (FTY), and 65 on cladribine (CLAD). The overall absolute reduction in the ARR over 4 years of treatment was higher in the second-line (FTY and CLAD) group (-2.00) compared with the first-line (-0.99) group (TFN and DMF). The total EDSS scores of patients who received FTY and CLAD were higher in the second (3.09, <i>p</i> = 0.024), third (3.94, <i>p</i> = 0.015), and fourth (3.6, <i>p</i> = 0.002) years of treatment, compared with the patients of first-line therapy. MRI revealed that the number of contrast-enhancing and new lesions was lower among patients taking second-line drugs in the second year (4.7% and 18.6%, respectively). The worst adherence to the drug therapy due to forgetfulness was observed in the DMF group (30.8%). Lymphopenia was less frequent in the TFN group (93.1%) and more frequent in the FTY group (86.5%) (<i>p</i> < 0.001). <i>Conclusions:</i> Over four years, second-line patients had greater ARR reduction, fewer MRI lesions, and higher EDSS from year two. DMF showed the lowest adherence, mainly due to patient forgetfulness, while lymphopenia occurred most frequently with FTY.