Prevalence of 2-year "No evidence of disease activity" (NEDA-3 and NEDA-4) in relapsing-remitting multiple sclerosis. A real-world study.

BACKGROUND: No evidence of disease activity (NEDA) is becoming a gold standard in the evaluation of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS). NEDA-3 status is the absence of relapses, new activity on brain MRI, and disability progression. NEDA-4 meets all NEDA-3 criteria plus lack of brain atrophy. OBJECTIVE: Aim of this study was to investigate the prevalence of two-year NEDA-3, NEDA-4, six-month delayed NEDA-3 (6mdNEDA-3), and six-month delayed NEDA-4 (6mdNEDA-4) in a cohort of patients with RRMS. Six-month delayed measures were introduced to consider latency of action of drugs. METHODS: Observational retrospective monocentric study. All the patients with RRMS starting DMT between 2015 and 2018, and with 2-year of follow-up, were included. Annualized brain volume loss (a-BVL) was calculated by SIENA software. RESULTS: We included 108 patients, the majority treated with first line DMT. At 2-year follow-up, 35 % of patients were NEDA-3 (50 % 6mdNEDA-3), and 17 % NEDA-4 (28 % 6mdNEDA-4). Loss of NEDA-3 status was mainly driven by MRI activity (70 %), followed by relapses (56 %), and only minimally by disability progression (7 %). CONCLUSION: In our cohort 2-year NEDA status, especially including lack of brain atrophy, was hard to achieve. Further studies are needed to establish the prognostic value of NEDA-3 and NEDA4 in the long-term follow-up.

The contribution of enhancing lesions in monitoring multiple sclerosis treatment: is gadolinium always necessary?

BACKGROUND: MRI is highly sensitive for monitoring of disease activity and treatment efficacy in MS. Patients treated with disease modifying therapy (DMT), who experience MRI activity, including contrast-enhancing lesions (CEL) or new/enlarged T2 lesions, should be evaluated for a switch to more effective treatment. Due to recent evidence of gadolinium (Gd) accumulation in the brain after repeated administration of Gd-based contrast agents, FDA recommended to limit its use. AIM: To investigate the proportion of cases in which MRI activity would be detectable only using contrast-enhanced T1-weighted sequences.Secondary aims were to assess the presence of clinical or demographic variables associated with reactivation of pre-existing lesions and to analyse therapeutic consequences of different types of MRI lesions. METHODS: We retrospectively evaluated brain MRI scans, performed between 2014 and 2018, in patients treated with DMT for at least 6 months. RESULTS: We analysed 906 scans in 255 patients. New/enlarged T2 lesions were detected in 13.7% of cases, CEL in 3.5%, CEL without new T2 lesions (old lesions reactivated) in 1.1%. No variables were associated with old lesions reactivated. CEL with T2 equivalent were at higher risk of DMT switch, compared with new/enlarged T2 lesions without corresponding CEL (OR 4.0, 95% CI 1.5-10.4, p  = 0.005). CONCLUSIONS: Reactivation of pre-existing lesions is limited to a tiny fraction of MRI studies. Gd + T1-weighted images could be omitted, in patients treated with DMT for at least 6 months, without relevant loss of information.