Real-world Safety and Efficacy of Dimethyl Fumarate in Relapse-Remitting Multiple Sclerosis Patients: A Regional Cohort Report of the Iranian Patients

Background: Real-world evidence evaluating the long-term effectiveness and safety of dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS) remains limited, particularly in Middle Eastern populations. Furthermore, whether previous exposure to disease-modifying therapies influences longitudinal treatment response has not been adequately characterized. We evaluated the real-world effectiveness, safety, and temporal treatment dynamics of DMF in RRMS and compared outcomes between treatment-naive and previously treated patients. Methods: This longitudinal observational cohort study enrolled 120 adults with RRMS initiating DMF (TECRA (R)) at two multiple sclerosis centers in Iran. Clinical outcomes, magnetic resonance imaging (MRI) activity, disability progression, and adverse events were assessed over 18 months at 6-month intervals. Repeated Expanded Disability Status Scale (EDSS) measurements were analyzed using linear mixed-effects models, while relapse counts and MRI lesion activity were evaluated using generalized estimating equations. Prespecified subgroup analyses examined differences according to prior treatment status. Results: Ninety-five patients completed the study. DMF produced a marked suppression of disease activity, reducing the annualized relapse rate by 95% (1.56 {+/-} 0.93 to 0.08 {+/-} 0.24; P < 0.001). EDSS improved during the first year and remained near baseline after 18 months despite a modest increase during the final follow-up interval. MRI inflammatory activity declined significantly throughout follow-up, although a mild increase in gadolinium-enhancing lesions after 12 months suggested possible attenuation of treatment effect over time. Overall, 88.4% of patients remained relapse-free, 70.5% demonstrated no MRI disease activity, and 64.2% achieved no evidence of disease activity (NEDA-3). While overall clinical outcomes were comparable between treatment-naive and previously treated patients, longitudinal analyses revealed distinct temporal patterns of MRI activity between groups. DMF was well tolerated, with predominantly mild cutaneous and gastrointestinal adverse events and infrequent treatment discontinuation. Conclusions: In conclusion, DMF was well tolerated and effective in reducing clinical and radiological disease activity. These findings support the long-term effectiveness of DMF in routine clinical practice while highlighting the importance of continued clinical and radiological monitoring to optimize individualized treatment strategies.