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

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

Disability outcomes in the N-MOmentum trial of inebilizumab in neuromyelitis optica spectrum disorder

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

Initial Acquisition of Mutans Streptococci by Infants: Evidence for a Discrete Window of Infectivity

Oral bacterial levels of 46 mother-child pairs were monitored from infant birth up to five years of age so that the acquisition of mutans streptococci (MS) by children could be studied. The initial acquisition of MS occurred in 38 children at the median age of 26 months during a discrete period we designated as the "window of infectivity". MS remained undetected in eight children (17%) until the end of the study period (median age of 56 mo). The levels of both MS and lactobacilli in saliva of mothers of children with and without MS were not significantly different. Comparisons between a caries-active cohort colonized by MS (nine of 38) and children without detectable MS revealed similar histories in terms of antibiotic usage, gestational age, and birth weight. Interestingly, half of the children between the ages of one and two years who were not colonized by MS were attended by caretakers other than the mother, while all of the caries-active children during this same time period were cared for by their mothers; the difference was statistically significant. Here we report for the first time that MS is acquired by infants during a defined period in the ontogeny of a child. Support for the notion of a discrete window of infectivity comes from other sources, including animal models. </jats:p