Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system characterized by recurrent inflammatory episodes and progressive neurodegeneration (Kappos et al., 2010). Disease-modifying therapies (DMTs) have substantially altered the natural history of MS by reducing relapse frequency, limiting new lesion formation, and delaying disability accumulation. Among these agents, fingolimod is a sphingosine-1-phosphate (S1P) receptor modulator that prevents lymphocyte egress from lymph nodes, thereby reducing central nervous system infiltration and inflammation (Druart et al., 2017).

The pivotal FREEDOMS and TRANSFORMS trials demonstrated that fingolimod significantly reduced annualized relapse rates (ARR), magnetic resonance imaging (MRI) activity, and risk of disability worsening compared with placebo or interferon beta-1a (Ziemssen et al., 2015; Biernacki et al., 2022; Comi et al., 2020). Extension studies confirmed its sustained efficacy over several years (Weinstock-Guttman et al., 2017; Kurtzke, 1983). Real-world data have supported these findings, showing favourable effectiveness and safety in broader patient populations, including those with high baseline disease activity and prior exposure to multiple therapies (Comi et al., 2020; Ziemssen et al., 2022; Biernacki et al., 2022); large observational programmes such as PANGEA have further underscored fingolimod’s durability and tolerability in routine practice.

Despite this, important knowledge gaps remain. Most studies have focused on outcomes after treatment initiation, whereas little is known about how trajectories of relapse and disability change when comparing the pre-treatment and post-treatment periods within the same patients. Such information is critical for understanding the full clinical impact of fingolimod beyond trial settings. Moreover, data in secondary progressive MS (SPMS) remain scarce. While fingolimod has shown benefits in controlling relapses, its effect on disability worsening in SPMS is less clear (Comi et al., 2020; ).

The present study addresses these gaps by evaluating a large, single-centre real-world cohort of patients with MS who were treated with fingolimod. We specifically compared relapse rates, disability outcomes, and NEDA-3 status over the three years before and after treatment initiation, with subgroup analyses for RRMS and SPMS. To our knowledge, this is one of the largest studies to directly contrast pre- and post-treatment trajectories within the same patients, providing a comprehensive perspective on fingolimod’s long-term effectiveness across different clinical phenotypes.