No Evident Disease Activity (NEDA): Associations with Brain Atrophy and Functional Outcomes in Patients from the Affirm Study
Objectives: To investigate the relationship between “no evident disease activity” (NEDA) and measures of brain atrophy and functional outcomes in patients with RRMS over 2 years in the AFFIRM study.
Methods: Natalizumab and placebo groups were combined. NEDA was defined as no relapse, no 12-week sustained Expanded Disability Status Scale (EDSS) progression, no gadolinium-enhancing lesions, and no new or enlarged T2 lesions. Percent changes in brain parenchymal fraction (BPF), changes in Paced Auditory Serial Addition Test-3 (PASAT), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9-HPT) as well as rates of confirmed EDSS improvement (12-week sustained decrease of ≥1.0 point) were compared in patients with and without NEDA.
Results: Overall, 27% of patients had NEDA over 2 years: 220 of 600 natalizumab-treated patients (37%) and 22 of 304 placebo-treated patients (7%). In the second year of the study, significantly smaller median percent reductions in BPF were seen in patients with NEDA (-0.15% vs -0.28%; P=0.0055) compared with patients who had any clinical or radiological disease activity. From baseline to 2 years, patients with NEDA had significantly better outcomes in PASAT (median change 2.00 with NEDA vs 1.00 without NEDA; P=0.0005), T25FW (median change 0.00 seconds with NEDA vs 0.20 seconds without NEDA; P<0.0001), and 9-HPT (median change -0.73 seconds with NEDA vs -0.24 seconds without NEDA; P<0.0001). The cumulative probability of EDSS improvement was 36.9% in patients with NEDA and 22.6% in patients with any disease activity (hazard ratio 1.918 [95% confidence interval: 1.374, 2.678]; P=0.0001).
Conclusions: Patients with NEDA showed smaller reductions in BPF, more improvement in disability, and better outcomes in cognitive function, walking speed, and upper extremity function, compared with patients with any evident disease activity.