For an N-MOmentum study of ibalizumab, a humanized anti-CD19 monoclonal antibody, in people with neuromyelitis optica spectrum disorder, treatment effects on EDSS score deterioration and modified Rankin Scale (mRS) scores were assessed (NMOSD). On days 1 and 15, adults (N=230) with aquaporin-4 immunoglobulin G-seropositive NMOSD or -seronegative neuromyelitis optica with an EDSS score of less than or equal to 8 were randomly (3:1) assigned to receive ibalizumab 300 mg or placebo. With the option to enter the ibalizumab open-label period, the randomized controlled period (RCP) lasted 28 weeks or until the adjudicated attack. A Cox proportional hazard model was used to estimate three-month EDSS-confirmed disability progression (CDP). Interaction tests were used to investigate the effect of baseline subgroups on impairment. The Wilcoxon-Mann-Whitney odds technique was used to assess mRS scores from the RCP. Inebilizumab reduced the risk of 3-months CDP compared to placebo (hazard ratio [HR]: 0.375; 95%CI:0.148-0.952;P=0.0390). The treatment effect determined with ibalizumab was unaffected by baseline disability, pre-research attack frequency, or disease duration (HRs:0.213-0.503; interaction tests: all (P>0.05), showing no effect of baseline variables on the outcome). Longer-term treatment improved mean EDSS scores. Participants who received ibalizumab at the end of the RCP were more likely to have a good mRS outcome (OR:1.663; 95%CI:1.195-2.385; p=0.0023). In people with NMOSD, ibalizumab had a better disability outcome than placebo.