Refining predictors of long-term NEDA-3 status in relapsing-remitting multiple sclerosis: insights from real-world data

BACKGROUND: No evidence of disease activity-3 (NEDA-3) constitutes a crucial target for relapsing-remitting multiple sclerosis (RRMS). Long-term predictors of its attainment remain insufficiently characterized. This study aimed to assess the prevalence and the predictors of long-term NEDA-3 status in a large real-world RRMS cohort. METHODS: This retrospective monocentric study analyzed RRMS patients strictly followed for up to six years. Treatment exposure was classified based on the efficacy of the first therapy in moderate (ME) and high efficacy (HE) disease modifying treatments (DMTs). Percentages of patients exposed to ME and HE DMTs reaching NEDA-3 were compared. Logistic regression models were applied to identify predictors of NEDA-3 achievement at 2 and 5 years. EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) were also analyzed in a small sub-cohort. RESULTS: 485 RRMS patients were included. Subjects starting treatment with HE DMTs were associated with significantly higher rates of NEDA-3 across all time-points. Significant risk factors for not achieving NEDA-3 included multifocal onset, delayed treatment initiation and spinal cord lesions. Conversely, treatment initiation with HE DMT was a significant protective factor for NEDA-3 status achievement at 2 and 5 years of follow-up. Early initiation of HE DMTs significantly improves long-term control of disease activity. CONCLUSIONS: Multifocal onset, delayed treatment initiation, presence of spinal cord lesions and oligoclonal bands were identified as risk factors of not achieving NEDA-3 status.