Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD

Abstract

Background: In the N-MOmentum trial, the risk of an adjudicated neuromyelitis optica spectrum disorder (NMOSD) attack was significantly reduced with inebilizumab compared with placebo. Objective: To demonstrate the robustness of this finding, using pre-specified sensitivity and subgroup analyses. Methods: N-MOmentum is a prospective, randomized, placebo-controlled, double-masked trial of inebilizumab, an anti-CD19 monoclonal B-cell-depleting antibody, in patients with NMOSD. Pre-planned and post hoc analyses were performed to evaluate the primary endpoint across a range of attack definitions and demographic groups, as well as key secondary endpoints. Results: In the N-MOmentum trial (ClinicalTrials.gov: NCT02200770), 174 participants received inebilizumab and 56 received placebo. Attack risk for inebilizumab versus placebo was consistently and significantly reduced, regardless of attack definition, type of attack, baseline disability, ethnicity, treatment history, or disease course (all with hazard ratios < 0.4 favoring inebilizumab, p < 0.05). Analyses of secondary endpoints showed similar trends. Conclusion: N-MOmentum demonstrated that inebilizumab provides a robust reduction in the risk of NMOSD attacks regardless of attack evaluation method, attack type, patient demographics, or previous therapy. The N-MOmentum study is registered at ClinicalTrials.gov: NCT2200770.

Neuromyelitis Optica Spectrum Disorder: Therapeutic Innovations and Complex Decision‐Making

“…Sensitivity analyses to test robustness of the primary endpoint were carried out in the PREVENT and N-MOmentum trials and corroborated the primary outcomes. 4,9 Inebilizumab also diminished the risk of 3-month confirmed disability progression independent of baseline features of the disease. 10 Importantly, there were differences regarding aquaporin-4 IgG serostatus.…”

Treatment and Relapse Prevention of Typical and Atypical Optic Neuritis

“…Due to the sample’s inequality regarding seronegative patients among groups (only four participants were randomized to the placebo arm), efficacy could not be interpreted in the seronegative subset. Of note, the trial also confirmed that the efficacy of inebulizumab was consistent across the clinical presentations of myelitis and optic neuritis domains [ 138 , 139 , 140 ].…”

“…Furthermore, among AQP4-seropositive patients, fewer had a statistically significant worsening of their EDSS score. The inebilizumab arm also had lower numbers of cumulative active MRI lesions and NMOSD-related hospitalizations compared with the placebo [ 139 , 140 , 141 ]. Serious adverse events were similar among both the inebulizumab (9%) and placebo groups (5%); however, 2% of patients on the agent developed transient grade 3 neutropenia.…”

“…The second patient, originally receiving inebilizumab, developed new neurological symptoms (weakness, aphasia, neurological decline, seizures) 9 days after receiving the maintenance dose. MRI showed new large lesions in white and grey matter, considered not representative for progressive multifocal leukoencephalopathy (PML), although one of three PCR tests on CSF was positive for JC virus, and brain biopsy was not performed; ultimately, the possibility that the death was treatment-related could not be excluded [ 140 , 141 ].…”

Monoclonal antibody drugs for the treatment of multiple sclerosis and neuromyelitis optica spectrum disorder

“…In other subgroup analyses, inebilizumab showed significant relapse inhibition compared to those given placebo regardless of the site of relapse, disease duration, number of relapses in the previous 6 mo, number of relapses since onset, baseline EDSS, race, weight, and previous immunosuppressive treatment, including rituximab. [45][46][47] In a continuation study, 201 AQP4 antibody-positive patients received inebilizumab (300 mg) every 26 wk, of which 75 patients had received the drug for more than 4 y. 48 In this report, 18 relapses were identified after the initiation of inebilizumab (annual relapse rate, 0.052), 12 of which (67%) occurred within 1 y of starting inebilizumab treatment, and four of the five severe relapses occurred within 1 y of starting inebilizumab treatment.…”