Abstract Details

Protein biomarkers related to cytokine signaling and inflammatory processes from placebo and inebilizumab treated participants were evaluated via multiplex immunoassay, (Olink®; Uppsala, Sweden) and biomarker (Simoa®; Lexington, MA, USA) panels. The Mann-Whitney test with a 10% false discovery rate (FDR) cutoff identified dysregulated proteins. Cytokine profiles were evaluated for correlation to longitudinal clinical endpoints, e.g., attack rate, MRI, hospitalizations, and disability.

At baseline, protein measurements were significantly dysregulated in 18/95 measurements for N-MOmentum participants (n=211) compared to healthy donors (HD, n=25). NMOSD vs HD results (median, p-value) included: IL-17a (pg/mL) 0.17 vs 0.08, p<0.0001; LAP-TGF-β-1 (NPX): 9.25 vs 8.73, p<0.0001; CXCL10 (NPX): 10.19 vs 9.55, p=0.001; IL-6 (pg/mL): 1.92 vs 1.25, p=0.01; IFN-γ (NPX): 7.16 vs 6.57, p=0.02. IL-17a was elevated in approximately 60% and IL-6, IFN-γ and CXCL10 in approximately 20% of participants. Evaluating the association of disease activity showed a weak correlation of IL-6 with Expanded Disability Status Scale (EDSS, R=0.27, p<0.0001) and SF36 PCS, (R=-0.21, p=0.002). Evaluating T2 MRI findings over the trial showed that IL-17a and IFN-γ were associated with increased new T2 findings at higher cytokine levels. Attack rate decreased for N-MOmentum participants regardless of baseline cytokine levels.

Pro-inflammatory cytokines were elevated in a subset of N-MOmentum participants at baseline including IL-6, IL-17a, and IFN inducible chemokines. Longitudinal analysis revealed a correlation with MRI findings over trial of N-MOmentum. Regardless of baseline cytokine levels, improvement in disease activity was observed with inebilizumab treatment.