The NEDA concept in MS was introduced in the Phase 3 AFFIRM study; use of BPF and sNfL together or instead of NEDA components is less studied.

All variables were obtained from AFFIRM using data for 537 NTZ- and 255 placebo-treated patients. Assessments included classical NEDA and neuroperformance (20% worsening on the PASAT [Paced Auditory Serial Addition Test], 9HPT [9-Hole Peg Test], and T25FW [Timed 25-Foot Walk] tests. Age-specific cut-points of sNfL levels were derived from healthy controls; patients with sNfL levels ≥ or < the age-specific 97.5th percentile were classified as having elevated or normal sNfL. Brain volume loss was defined as change in BPF < –0.2%/year. Change was assessed from baseline to Year 2 for all measures except BPF (Year 1–2). Comparisons included odds ratios (ORs) and area under the receiver-operating characteristic curve (AUC). Multivariate logistic regression was used to determine which measures independently discriminated treatment groups. Composites were compared to NEDA.

Univariate analysis showed that measures with the strongest association with NTZ treatment (OR; AUC; p-value vs. placebo) were MRI activity (9.3; 0.73; p < 0.0001), relapses (2.7; 0.62; p < 0.0001), and sNfL (6.1; 0.65; p < 0.0001). Best fit multivariate logistic regression model included (OR; 95% CI): MRI activity (7.2; 4.7–10.9), sNfL (4.1; 2.6–6.2), and relapses (2.1; 1.5–3.0; p < 0.0001 for each variable).

Analysis of AFFIRM data revealed that MRI activity, sNfL, and relapses had the strongest association with NTZ treatment over 2 years and achieved similar treatment group discrimination as NEDA.