2024 American Academy of Neurology Abstract Website

Sean Pittock¹, Orhan Aktas², Ho Jin Kim³, Romain Marignier⁴, Dean Wingerchuk⁵, Micheal Smith⁶, Kristen Clarkson⁶, William Rees⁶, Kristina Patterson⁶, Bruce Cree⁷
¹Mayo Clinic and Center for MS and Autoimmune Neurology, Rochester, MN, USA, ²Medical Facility, Heinrich Heine University Düsseldorf, Düsseldorf, Germany, ³Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea, ⁴Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuroinflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France, ⁵Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA, ⁶Amgen Research, Amgen Inc, Thousand Oaks, CA, USA, ⁷Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA

Objective:

To evaluate the relationship between cytokine levels and disease activity in Neuromyelitis Optica Spectrum Disorder (NMOSD) participants from N-MOmentum (NCT02200770).

Background:

NMOSD is a chronic, autoimmune disease characterized by recurrent attacks on the central nervous system causing permanent neurological damage and cumulative disability. Cytokine levels increase in rheumatologic diseases; however, limited information exists about these levels in NMOSD.

Design/Methods:

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.

Results:

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.

Conclusions:

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.