Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder

Abstract

Objective: To assess treatment effects on Expanded Disability Status Scale (EDSS) score worsening and modified Rankin Scale (mRS) scores in the N-MOmentum trial of inebilizumab, a humanized anti-CD19 monoclonal antibody, in participants with neuromyelitis optica spectrum disorder (NMOSD).

Methods: Adults (N = 230) with aquaporin-4 immunoglobulin G-seropositive NMOSD or -seronegative neuromyelitis optica and an EDSS score ≤8 were randomized (3:1) to receive inebilizumab 300 mg or placebo on days 1 and 15. The randomized controlled period (RCP) was 28 weeks or until adjudicated attack, with an option to enter the inebilizumab open-label period. Three-month EDSS-confirmed disability progression (CDP) was assessed using a Cox proportional hazard model. The effect of baseline subgroups on disability was assessed by interaction tests. mRS scores from the RCP were analyzed by the Wilcoxon-Mann-Whitney odds approach.

Results: Compared with placebo, inebilizumab reduced the risk of 3-month CDP (hazard ratio [HR]: 0.375; 95% CI: 0.148-0.952; p = 0.0390). Baseline disability, prestudy attack frequency, and disease duration did not affect the treatment effect observed with inebilizumab (HRs: 0.213-0.503; interaction tests: all p > 0.05, indicating no effect of baseline covariates on outcome). Mean EDSS scores improved with longer-term treatment. Inebilizumab-treated participants were more likely to have a favorable mRS outcome at the end of the RCP (OR: 1.663; 95% CI: 1.195-2.385; p = 0.0023).

Conclusions: Disability outcomes were more favorable with inebilizumab vs placebo in participants with NMOSD.

Classification of evidence: This study provides Class II evidence that for patients with NMOSD, inebilizumab reduces the risk of worsening disability. N-MOmentum is registered at ClinicalTrials.gov: NCT02200770.

Figure 1. Post Hoc Analyses of EDSS Outcomes

(A) EDSS worsening at the end of the RCP using nonattack visit data. Analysis conducted by using EDSS values from OLP month 3 for those participants who had AC-determined attack at their end of RCP visit (placebo: n = 15; inebilizumab: n = 14). End of the RCP visit data were used for those who did not have attacks (placebo: n = 0; inebilizumab: n = 2). (B) Three-month CDP from the end of the RCP visit. Analysis conducted for the subgroup of patients with EDSS worsening at the last RCP visit irrespective of whether participants had attacks, confirmed at OLP month 3 (placebo: 7/7 had attacks; inebilizumab: 2/6 had attacks). (C) Kaplan-Meier plot of the risk of 3-month CDP from any point in the RCP. None of those randomized to placebo with EDSS worsening at the last RCP visit had a subsequent attack in the first 3 months of OLP. Only 1 participant randomized to inebilizumab with EDSS worsening at the last RCP visit had a subsequent attack within the 3-month OLP window. AC = adjudication committee; CDP = confirmed disability progression; EDSS = Expanded Disability Status Scale; HR = hazard ratio; OLP = open-label period; RCP = randomized controlled period.

Figure 2. Subgroup Analyses of EDSS Outcomes

Figure shows the risk of EDSS score worsening from baseline to the end of the RCP. EDSS = Expanded Disability Status Scale; HR = hazard ratio; RCP = randomized controlled period.

Figure 3. Post Hoc Analysis of Change in Mean EDSS Scores During the RCP and OLP

(A) Overall population. (B) Participants with attacks in the RCP. (C) Participants without attacks in the RCP. EDSS = Expanded Disability Status Scale; OLP = open-label period; RCP = randomized controlled period.

Figure 4. mRS Outcomes During the RCP

(A) Treatment effect based on the mRS score during the RCP. (B) Distribution of mRS scores at baseline and at the last RCP visit in patients treated with placebo. (C) Distribution of mRS scores at baseline and at the last RCP visit in patients treated with inebilizumab. mRS = modified Rankin Scale; RCP = randomized controlled period; WMWodds = Wilcoxon-Mann-Whitney odds.