Beyond Efficacy: Persistence, NEDA, and Therapeutic Decision-Making in First-Line Multiple Sclerosis Treatment

Injectable drugs, including interferon-beta and glatiramer acetate (collectively referred to as BRACE), dimethyl fumarate (DMF), and teriflunomide (TER) are commonly used as initial disease-modifying therapies (DMTs) for multiple sclerosis (MS), especially in patients with favorable prognostic profiles. Despite their continued use, real-world comparative data on long-term treatment persistence and comprehensive disease control remain limited.

This retrospective study analyzed 400 patients initiating BRACE (n = 132), DMF (n = 130), or TER (n = 138) between 2014 and 2024 in routine clinical practice. Persistence was defined as treatment continuation without interruptions for ≥ 6 months. Effectiveness was evaluated using cumulative no evidence of disease activity (NEDA)-2 and NEDA-3 status. NEDA-2 included the absence of clinical relapses and confirmed disability progression; NEDA-3 additionally required the lack of MRI activity. Loss of NEDA status was marked from the first occurrence of any criterion failure.

Injectables showed significantly higher discontinuation rates (70.5%) compared to patients with TER (42.0%) and DMF (48.5%) (p < 0.001), with divergence evident after year 3. Median time to discontinuation was 3.55 years for BRACE, 4.88 years for TER, and 5.78 years for DMF. No significant differences were observed in NEDA-2 or NEDA-3 survival. Patients with TER showed higher NEDA-2 rates at 1 year (87%) than DMF (74%) and BRACE (77%) (p < 0.05), but this difference was not sustained over time.

In real-world practice, oral therapies tend to be associated with better long-term persistence than injectables, while effectiveness measured by cumulative NEDA-3 remains comparable. These findings highlight the role of patient-centered factors such as tolerability and administration route in treatment adherence, supporting cumulative NEDA as a meaningful outcome in clinical decision-making.